The Experts below are selected from a list of 5100 Experts worldwide ranked by ideXlab platform
Edward Balish - One of the best experts on this subject based on the ideXlab platform.
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susceptibility of germfree phagocyte oxidase and nitric oxide synthase 2 deficient mice defective in the production of reactive metabolites of both oxygen and nitrogen to mucosal and Systemic Candidiasis of endogenous origin
Infection and Immunity, 2005Co-Authors: Edward Balish, Thomas F Warner, Peter J Nicholas, Emily E Paulling, Caroline Westwater, David A SchofieldAbstract:Mice deficient for phagocyte oxidase (Phox) and nitric oxide synthase 2 (NOS2) (gp91phox−/−/NOS2−/−), defective in the production of both reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI), were used to investigate the role of phagocytic cells during mucosal and Systemic Candidiasis of endogenous origin. The alimentary tracts of germfree mice were colonized with Candida albicans wild type or each of two hyphal signaling-defective mutants (efg1/efg1 and efg1/efg1 cph1/cph1). All Candida-colonized gp91phox−/−/NOS2−/− mice were moribund within 12 to 15 days after oral inoculation. C. albicans wild-type and mutant strains colonized the alimentary tracts equally well and were able to translocate, most likely via Peyer's patches and mesenteric lymph nodes, to the internal organs and trigger the formation of abscesses; however, the wild-type and mutant strains did not survive in the abscessed murine tissues. Surprisingly, there was no significant difference in the ability of peritoneal exudate cells from gp91phox−/−/NOS2−/−, NOS2−/−, gp91phox−/−, or immunocompetent C57BL/6 mice to kill C. albicans in vitro. This suggests that anti-Candida factors other than ROI and RNI can control the growth of C. albicans and that gp91phox−/−/NOS2−/− mice die due to the inability of the host to control its inflammatory response to Candida. Correspondingly, reverse transcription-PCR analysis showed increased expression of the cytokines gamma interferon, tumor necrosis factor alpha, and the chemokines MIP-2 and KC at the site of infection, while interleukin-15 expression remained relatively unchanged between germfree and infected tissues. These studies indicate that defects in ROI and RNI enabled C. albicans to translocate and disseminate to the internal organs, resulting in an uncontrolled immune response, severe pathology, and death; however, ROI and RNI were not required for the killing of phagocytized C. albicans, indicating that other anti-Candida factors either compensate or are sufficient for the killing of phagocytized Candida.
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disparate requirement for t cells in resistance to mucosal and acute Systemic Candidiasis
Infection and Immunity, 2000Co-Authors: Jessica Jonescarson, Andres Vazqueztorres, Thomas F Warner, Edward BalishAbstract:Although highly susceptible to orogastric Candidiasis, T-cell receptor δ- and α-chain knockout mice, deficient in γδ and αβ T cells, respectively, were found to be resistant to disseminated Candidiasis of endogenous origin and to acute Systemic Candidiasis (resulting from intravenous injection).
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mucosal and Systemic Candidiasis in il 8rh balb c mice
Journal of Leukocyte Biology, 1999Co-Authors: Edward Balish, R D Wagner, Andres Vazqueztorres, Jessica Jonescarson, C Pierson, Thomas F WarnerAbstract:Germ-free BALB/c mice, genetically engineered to be deficient for interleukin-8 (IL-8) receptor homolog (IL-8Rh-/-), were more susceptible to gastric Candidiasis after oral challenge and to acute Systemic Candidiasis after intravenous challenge than IL-8Rh+/+ controls. In comparison to IL-8Rh+/+ mice, the IL-8Rh-/- mice had slower influx of polymorphonuclear neutrophils (PMN) into Candida albicans-infected tissues and a lower percentage of PMN in peritoneal exudate cells (PEC) elicited with heat-killed C. albicans. PEC from IL-8Rh-/- mice exhibited less luminol-dependent chemiluminescence in response to C. albicans and did not kill C. albicans hyphae as well as PEC from IL-8Rh+/+ mice. C. albicans-colonized IL-8Rh-/- mice showed no histological evidence of Systemic Candidiasis. These results suggest a role for the IL-8Rh in murine resistance to gastric and acute Systemic Candidiasis, but not in resistance to Systemic Candidiasis of endogenous origin.
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early resistance of interleukin 10 knockout mice to acute Systemic Candidiasis
Infection and Immunity, 1999Co-Authors: Andres Vazqueztorres, R D Wagner, Jessica Jonescarson, Thomas F Warner, Edward BalishAbstract:In contrast to immunocompetent controls, interleukin-10 (IL-10) knockout (KO) mice eliminated an experimental intravenous inoculation with Candida albicans from their kidneys. Improved clearance of C. albicans from the kidneys of IL-10 KO mice was evident at 24 h after intravenous challenge with the fungus. Conversely, mice with a deletion of the IL-4 cytokine gene were more susceptible to Systemic Candidiasis than were immunocompetent controls. The hyperresistance of IL-10 KO mice to acute Systemic Candidiasis did not seem to correlate with nitric oxide-mediated immunity, but rather, it appeared to be associated with more efficient effector function of innate cells, possibly neutrophils. In support of the latter hypothesis, we observed that neutrophils from IL-10 KO mice were more efficient at killing C. albicans blastoconidia and hyphae than were neutrophils from immunocompetent control mice. Neither IL-10 KO nor IL-4 KO mice that were monoassociated with C. albicans for 4 weeks showed any histologic evidence of Systemic Candidiasis of endogenous origin. In contrast to Systemic Candidiasis, we observed no significant (P < 0.05) differences in susceptibility among IL-10 KO, IL-4 KO, and wild-type (immunocompetent) mice to orogastric Candidiasis. Our results suggest that IL-10 exerts a negative effect on the early, innate response to acute Systemic Candidiasis; however, in comparison to immunocompetent control (wild-type) mice, neither IL-10 nor IL-4 deficiency enhanced susceptibility to orogastric Candidiasis.
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b cell knockout mice are resistant to mucosal and Systemic Candidiasis of endogenous origin but susceptible to experimental Systemic Candidiasis
The Journal of Infectious Diseases, 1996Co-Authors: Doug R Wagner, Jessica Jonescarson, Andres Vazqueztorres, Thomas F Warner, Edward BalishAbstract:Germfree JHD mice, which lack functional B cells and antibodies, were as resistant to orogastric and disseminated Candidiasis of endogenous origin as were immunocompetent controls. Newborn J HD mice, in contrast to adult mice, were resistant to alimentary tract colonization by Candida albicans for 5-7 days after birth. C. albicans-colonizedJHD mice were more resistant to intravenous challenge with C. albicans and had greater splenocyte proliferative responses to C. albicans antigens than did germfree mice or conventional controls. Thus, innate and acquired T cell-mediated immune responses induced after oral immunization are sufficient to protect J HD mice from mucosal and Systemic Candidiasis of endogenous origin; however, functional B cells may be required to protect mice from a primary intravenous challenge with C. albicans. The role of antibody-mediated immunity (AMI) in host de fense against Candida albicans infections is controversial [1]. Numerous clinical observations suggest that innate and cell mediated immunity (CMI) are more important than AMI in resistance to Candidiasis [2]. Most patients with Candidiasis are neutropenic [3], T cell-deficient, or both; however, most have demonstrable levels of serum antibodies to C. albicans [4]. Patients with congenital defects in AMI (e.g., X-linked agam maglobulinemia and secretory IgA deficiency) but intact CMI are not overly susceptible to mucosal or Systemic Candidiasis [5]. Conversely, recent investigations suggest that antibodies to heat-shock proteins [6] or to specific C. albicans surface antigens [7] play a role in resistance to Systemic Candidiasis. Studies with laboratory animals have not resolved the role of AMI in resistance to Candidiasis. Investigations in mice immunized with C. albicans antigens or treated with high titered immune serum suggest that antibodies are protective [7~ 10] or have no effect [11-13] on murine susceptibility to experimental Systemic Candidiasis. Although immunocompetent mice and an intravenous (iv) challenge route have been used in most studies designed to assess the efficacy of antibody in resistance to Candidiasis, several studies have used congenitally immunodeficient mice (T or B cell-mediated immunity). Athymic mice with de fects in thymus-matured T cells and production of T cell dependent antibodies [14], severe combined immunodefi cient (SCID) mice with defects in T and B cell functions
Andres Vazqueztorres - One of the best experts on this subject based on the ideXlab platform.
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disparate requirement for t cells in resistance to mucosal and acute Systemic Candidiasis
Infection and Immunity, 2000Co-Authors: Jessica Jonescarson, Andres Vazqueztorres, Thomas F Warner, Edward BalishAbstract:Although highly susceptible to orogastric Candidiasis, T-cell receptor δ- and α-chain knockout mice, deficient in γδ and αβ T cells, respectively, were found to be resistant to disseminated Candidiasis of endogenous origin and to acute Systemic Candidiasis (resulting from intravenous injection).
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mucosal and Systemic Candidiasis in il 8rh balb c mice
Journal of Leukocyte Biology, 1999Co-Authors: Edward Balish, R D Wagner, Andres Vazqueztorres, Jessica Jonescarson, C Pierson, Thomas F WarnerAbstract:Germ-free BALB/c mice, genetically engineered to be deficient for interleukin-8 (IL-8) receptor homolog (IL-8Rh-/-), were more susceptible to gastric Candidiasis after oral challenge and to acute Systemic Candidiasis after intravenous challenge than IL-8Rh+/+ controls. In comparison to IL-8Rh+/+ mice, the IL-8Rh-/- mice had slower influx of polymorphonuclear neutrophils (PMN) into Candida albicans-infected tissues and a lower percentage of PMN in peritoneal exudate cells (PEC) elicited with heat-killed C. albicans. PEC from IL-8Rh-/- mice exhibited less luminol-dependent chemiluminescence in response to C. albicans and did not kill C. albicans hyphae as well as PEC from IL-8Rh+/+ mice. C. albicans-colonized IL-8Rh-/- mice showed no histological evidence of Systemic Candidiasis. These results suggest a role for the IL-8Rh in murine resistance to gastric and acute Systemic Candidiasis, but not in resistance to Systemic Candidiasis of endogenous origin.
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early resistance of interleukin 10 knockout mice to acute Systemic Candidiasis
Infection and Immunity, 1999Co-Authors: Andres Vazqueztorres, R D Wagner, Jessica Jonescarson, Thomas F Warner, Edward BalishAbstract:In contrast to immunocompetent controls, interleukin-10 (IL-10) knockout (KO) mice eliminated an experimental intravenous inoculation with Candida albicans from their kidneys. Improved clearance of C. albicans from the kidneys of IL-10 KO mice was evident at 24 h after intravenous challenge with the fungus. Conversely, mice with a deletion of the IL-4 cytokine gene were more susceptible to Systemic Candidiasis than were immunocompetent controls. The hyperresistance of IL-10 KO mice to acute Systemic Candidiasis did not seem to correlate with nitric oxide-mediated immunity, but rather, it appeared to be associated with more efficient effector function of innate cells, possibly neutrophils. In support of the latter hypothesis, we observed that neutrophils from IL-10 KO mice were more efficient at killing C. albicans blastoconidia and hyphae than were neutrophils from immunocompetent control mice. Neither IL-10 KO nor IL-4 KO mice that were monoassociated with C. albicans for 4 weeks showed any histologic evidence of Systemic Candidiasis of endogenous origin. In contrast to Systemic Candidiasis, we observed no significant (P < 0.05) differences in susceptibility among IL-10 KO, IL-4 KO, and wild-type (immunocompetent) mice to orogastric Candidiasis. Our results suggest that IL-10 exerts a negative effect on the early, innate response to acute Systemic Candidiasis; however, in comparison to immunocompetent control (wild-type) mice, neither IL-10 nor IL-4 deficiency enhanced susceptibility to orogastric Candidiasis.
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b cell knockout mice are resistant to mucosal and Systemic Candidiasis of endogenous origin but susceptible to experimental Systemic Candidiasis
The Journal of Infectious Diseases, 1996Co-Authors: Doug R Wagner, Jessica Jonescarson, Andres Vazqueztorres, Thomas F Warner, Edward BalishAbstract:Germfree JHD mice, which lack functional B cells and antibodies, were as resistant to orogastric and disseminated Candidiasis of endogenous origin as were immunocompetent controls. Newborn J HD mice, in contrast to adult mice, were resistant to alimentary tract colonization by Candida albicans for 5-7 days after birth. C. albicans-colonizedJHD mice were more resistant to intravenous challenge with C. albicans and had greater splenocyte proliferative responses to C. albicans antigens than did germfree mice or conventional controls. Thus, innate and acquired T cell-mediated immune responses induced after oral immunization are sufficient to protect J HD mice from mucosal and Systemic Candidiasis of endogenous origin; however, functional B cells may be required to protect mice from a primary intravenous challenge with C. albicans. The role of antibody-mediated immunity (AMI) in host de fense against Candida albicans infections is controversial [1]. Numerous clinical observations suggest that innate and cell mediated immunity (CMI) are more important than AMI in resistance to Candidiasis [2]. Most patients with Candidiasis are neutropenic [3], T cell-deficient, or both; however, most have demonstrable levels of serum antibodies to C. albicans [4]. Patients with congenital defects in AMI (e.g., X-linked agam maglobulinemia and secretory IgA deficiency) but intact CMI are not overly susceptible to mucosal or Systemic Candidiasis [5]. Conversely, recent investigations suggest that antibodies to heat-shock proteins [6] or to specific C. albicans surface antigens [7] play a role in resistance to Systemic Candidiasis. Studies with laboratory animals have not resolved the role of AMI in resistance to Candidiasis. Investigations in mice immunized with C. albicans antigens or treated with high titered immune serum suggest that antibodies are protective [7~ 10] or have no effect [11-13] on murine susceptibility to experimental Systemic Candidiasis. Although immunocompetent mice and an intravenous (iv) challenge route have been used in most studies designed to assess the efficacy of antibody in resistance to Candidiasis, several studies have used congenitally immunodeficient mice (T or B cell-mediated immunity). Athymic mice with de fects in thymus-matured T cells and production of T cell dependent antibodies [14], severe combined immunodefi cient (SCID) mice with defects in T and B cell functions
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poly i c induced interferons enhance susceptibility of scid mice to Systemic Candidiasis
Infection and Immunity, 1992Co-Authors: Jani R Jensen, Andres Vazqueztorres, Edward BalishAbstract:In the absence of any demonstrable T- or B-cell responses, gnotobiotic CB-17 SCID (severe combined immunodeficient) mice not only show innate resistance to acute Systemic (intravenous challenge) Candidiasis but also manifest innate resistance to Systemic Candidiasis of endogenous (gastrointestinal tract) origin. Poly(I. C), a potent inducer of interferons (IFNs) in vivo, enhanced the susceptibility of CB-17 SCID mice to acute Systemic Candidiasis and to Systemic Candidiasis of endogenous origin, as demonstrated by increased numbers of viable Candida albicans in internal organs after poly(I. C) treatment. The poly(I. C)-enhanced susceptibility of mice to Candidiasis was abrogated by in vivo treatment with antibodies to IFN-alpha, -beta, and -gamma. In vivo depletion of natural killer cells from SCID mice did not significantly enhance their susceptibility to Systemic Candidiasis or abrogate poly(I. C)-enhanced susceptibility. In vivo and in vitro, treatment with poly(I. C) impaired the candidacidal and phagocytic activity of thioglycollate-elicited macrophages from SCID mice. Antibody to IFN-alpha/beta or IFN-beta alone interfered with the ability of poly(I. C) to impair the candidacidal activity of macrophages from SCID mice in vitro. These data suggest that poly(I. C)-induced interferons can impair the candidacidal activity of macrophages in SCID mice and decrease their innate resistance to acute Systemic Candidiasis and to Systemic Candidiasis of endogenous origin.
Thomas F Warner - One of the best experts on this subject based on the ideXlab platform.
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susceptibility of germfree phagocyte oxidase and nitric oxide synthase 2 deficient mice defective in the production of reactive metabolites of both oxygen and nitrogen to mucosal and Systemic Candidiasis of endogenous origin
Infection and Immunity, 2005Co-Authors: Edward Balish, Thomas F Warner, Peter J Nicholas, Emily E Paulling, Caroline Westwater, David A SchofieldAbstract:Mice deficient for phagocyte oxidase (Phox) and nitric oxide synthase 2 (NOS2) (gp91phox−/−/NOS2−/−), defective in the production of both reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI), were used to investigate the role of phagocytic cells during mucosal and Systemic Candidiasis of endogenous origin. The alimentary tracts of germfree mice were colonized with Candida albicans wild type or each of two hyphal signaling-defective mutants (efg1/efg1 and efg1/efg1 cph1/cph1). All Candida-colonized gp91phox−/−/NOS2−/− mice were moribund within 12 to 15 days after oral inoculation. C. albicans wild-type and mutant strains colonized the alimentary tracts equally well and were able to translocate, most likely via Peyer's patches and mesenteric lymph nodes, to the internal organs and trigger the formation of abscesses; however, the wild-type and mutant strains did not survive in the abscessed murine tissues. Surprisingly, there was no significant difference in the ability of peritoneal exudate cells from gp91phox−/−/NOS2−/−, NOS2−/−, gp91phox−/−, or immunocompetent C57BL/6 mice to kill C. albicans in vitro. This suggests that anti-Candida factors other than ROI and RNI can control the growth of C. albicans and that gp91phox−/−/NOS2−/− mice die due to the inability of the host to control its inflammatory response to Candida. Correspondingly, reverse transcription-PCR analysis showed increased expression of the cytokines gamma interferon, tumor necrosis factor alpha, and the chemokines MIP-2 and KC at the site of infection, while interleukin-15 expression remained relatively unchanged between germfree and infected tissues. These studies indicate that defects in ROI and RNI enabled C. albicans to translocate and disseminate to the internal organs, resulting in an uncontrolled immune response, severe pathology, and death; however, ROI and RNI were not required for the killing of phagocytized C. albicans, indicating that other anti-Candida factors either compensate or are sufficient for the killing of phagocytized Candida.
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disparate requirement for t cells in resistance to mucosal and acute Systemic Candidiasis
Infection and Immunity, 2000Co-Authors: Jessica Jonescarson, Andres Vazqueztorres, Thomas F Warner, Edward BalishAbstract:Although highly susceptible to orogastric Candidiasis, T-cell receptor δ- and α-chain knockout mice, deficient in γδ and αβ T cells, respectively, were found to be resistant to disseminated Candidiasis of endogenous origin and to acute Systemic Candidiasis (resulting from intravenous injection).
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mucosal and Systemic Candidiasis in il 8rh balb c mice
Journal of Leukocyte Biology, 1999Co-Authors: Edward Balish, R D Wagner, Andres Vazqueztorres, Jessica Jonescarson, C Pierson, Thomas F WarnerAbstract:Germ-free BALB/c mice, genetically engineered to be deficient for interleukin-8 (IL-8) receptor homolog (IL-8Rh-/-), were more susceptible to gastric Candidiasis after oral challenge and to acute Systemic Candidiasis after intravenous challenge than IL-8Rh+/+ controls. In comparison to IL-8Rh+/+ mice, the IL-8Rh-/- mice had slower influx of polymorphonuclear neutrophils (PMN) into Candida albicans-infected tissues and a lower percentage of PMN in peritoneal exudate cells (PEC) elicited with heat-killed C. albicans. PEC from IL-8Rh-/- mice exhibited less luminol-dependent chemiluminescence in response to C. albicans and did not kill C. albicans hyphae as well as PEC from IL-8Rh+/+ mice. C. albicans-colonized IL-8Rh-/- mice showed no histological evidence of Systemic Candidiasis. These results suggest a role for the IL-8Rh in murine resistance to gastric and acute Systemic Candidiasis, but not in resistance to Systemic Candidiasis of endogenous origin.
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early resistance of interleukin 10 knockout mice to acute Systemic Candidiasis
Infection and Immunity, 1999Co-Authors: Andres Vazqueztorres, R D Wagner, Jessica Jonescarson, Thomas F Warner, Edward BalishAbstract:In contrast to immunocompetent controls, interleukin-10 (IL-10) knockout (KO) mice eliminated an experimental intravenous inoculation with Candida albicans from their kidneys. Improved clearance of C. albicans from the kidneys of IL-10 KO mice was evident at 24 h after intravenous challenge with the fungus. Conversely, mice with a deletion of the IL-4 cytokine gene were more susceptible to Systemic Candidiasis than were immunocompetent controls. The hyperresistance of IL-10 KO mice to acute Systemic Candidiasis did not seem to correlate with nitric oxide-mediated immunity, but rather, it appeared to be associated with more efficient effector function of innate cells, possibly neutrophils. In support of the latter hypothesis, we observed that neutrophils from IL-10 KO mice were more efficient at killing C. albicans blastoconidia and hyphae than were neutrophils from immunocompetent control mice. Neither IL-10 KO nor IL-4 KO mice that were monoassociated with C. albicans for 4 weeks showed any histologic evidence of Systemic Candidiasis of endogenous origin. In contrast to Systemic Candidiasis, we observed no significant (P < 0.05) differences in susceptibility among IL-10 KO, IL-4 KO, and wild-type (immunocompetent) mice to orogastric Candidiasis. Our results suggest that IL-10 exerts a negative effect on the early, innate response to acute Systemic Candidiasis; however, in comparison to immunocompetent control (wild-type) mice, neither IL-10 nor IL-4 deficiency enhanced susceptibility to orogastric Candidiasis.
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b cell knockout mice are resistant to mucosal and Systemic Candidiasis of endogenous origin but susceptible to experimental Systemic Candidiasis
The Journal of Infectious Diseases, 1996Co-Authors: Doug R Wagner, Jessica Jonescarson, Andres Vazqueztorres, Thomas F Warner, Edward BalishAbstract:Germfree JHD mice, which lack functional B cells and antibodies, were as resistant to orogastric and disseminated Candidiasis of endogenous origin as were immunocompetent controls. Newborn J HD mice, in contrast to adult mice, were resistant to alimentary tract colonization by Candida albicans for 5-7 days after birth. C. albicans-colonizedJHD mice were more resistant to intravenous challenge with C. albicans and had greater splenocyte proliferative responses to C. albicans antigens than did germfree mice or conventional controls. Thus, innate and acquired T cell-mediated immune responses induced after oral immunization are sufficient to protect J HD mice from mucosal and Systemic Candidiasis of endogenous origin; however, functional B cells may be required to protect mice from a primary intravenous challenge with C. albicans. The role of antibody-mediated immunity (AMI) in host de fense against Candida albicans infections is controversial [1]. Numerous clinical observations suggest that innate and cell mediated immunity (CMI) are more important than AMI in resistance to Candidiasis [2]. Most patients with Candidiasis are neutropenic [3], T cell-deficient, or both; however, most have demonstrable levels of serum antibodies to C. albicans [4]. Patients with congenital defects in AMI (e.g., X-linked agam maglobulinemia and secretory IgA deficiency) but intact CMI are not overly susceptible to mucosal or Systemic Candidiasis [5]. Conversely, recent investigations suggest that antibodies to heat-shock proteins [6] or to specific C. albicans surface antigens [7] play a role in resistance to Systemic Candidiasis. Studies with laboratory animals have not resolved the role of AMI in resistance to Candidiasis. Investigations in mice immunized with C. albicans antigens or treated with high titered immune serum suggest that antibodies are protective [7~ 10] or have no effect [11-13] on murine susceptibility to experimental Systemic Candidiasis. Although immunocompetent mice and an intravenous (iv) challenge route have been used in most studies designed to assess the efficacy of antibody in resistance to Candidiasis, several studies have used congenitally immunodeficient mice (T or B cell-mediated immunity). Athymic mice with de fects in thymus-matured T cells and production of T cell dependent antibodies [14], severe combined immunodefi cient (SCID) mice with defects in T and B cell functions
Jessica Jonescarson - One of the best experts on this subject based on the ideXlab platform.
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disparate requirement for t cells in resistance to mucosal and acute Systemic Candidiasis
Infection and Immunity, 2000Co-Authors: Jessica Jonescarson, Andres Vazqueztorres, Thomas F Warner, Edward BalishAbstract:Although highly susceptible to orogastric Candidiasis, T-cell receptor δ- and α-chain knockout mice, deficient in γδ and αβ T cells, respectively, were found to be resistant to disseminated Candidiasis of endogenous origin and to acute Systemic Candidiasis (resulting from intravenous injection).
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mucosal and Systemic Candidiasis in il 8rh balb c mice
Journal of Leukocyte Biology, 1999Co-Authors: Edward Balish, R D Wagner, Andres Vazqueztorres, Jessica Jonescarson, C Pierson, Thomas F WarnerAbstract:Germ-free BALB/c mice, genetically engineered to be deficient for interleukin-8 (IL-8) receptor homolog (IL-8Rh-/-), were more susceptible to gastric Candidiasis after oral challenge and to acute Systemic Candidiasis after intravenous challenge than IL-8Rh+/+ controls. In comparison to IL-8Rh+/+ mice, the IL-8Rh-/- mice had slower influx of polymorphonuclear neutrophils (PMN) into Candida albicans-infected tissues and a lower percentage of PMN in peritoneal exudate cells (PEC) elicited with heat-killed C. albicans. PEC from IL-8Rh-/- mice exhibited less luminol-dependent chemiluminescence in response to C. albicans and did not kill C. albicans hyphae as well as PEC from IL-8Rh+/+ mice. C. albicans-colonized IL-8Rh-/- mice showed no histological evidence of Systemic Candidiasis. These results suggest a role for the IL-8Rh in murine resistance to gastric and acute Systemic Candidiasis, but not in resistance to Systemic Candidiasis of endogenous origin.
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early resistance of interleukin 10 knockout mice to acute Systemic Candidiasis
Infection and Immunity, 1999Co-Authors: Andres Vazqueztorres, R D Wagner, Jessica Jonescarson, Thomas F Warner, Edward BalishAbstract:In contrast to immunocompetent controls, interleukin-10 (IL-10) knockout (KO) mice eliminated an experimental intravenous inoculation with Candida albicans from their kidneys. Improved clearance of C. albicans from the kidneys of IL-10 KO mice was evident at 24 h after intravenous challenge with the fungus. Conversely, mice with a deletion of the IL-4 cytokine gene were more susceptible to Systemic Candidiasis than were immunocompetent controls. The hyperresistance of IL-10 KO mice to acute Systemic Candidiasis did not seem to correlate with nitric oxide-mediated immunity, but rather, it appeared to be associated with more efficient effector function of innate cells, possibly neutrophils. In support of the latter hypothesis, we observed that neutrophils from IL-10 KO mice were more efficient at killing C. albicans blastoconidia and hyphae than were neutrophils from immunocompetent control mice. Neither IL-10 KO nor IL-4 KO mice that were monoassociated with C. albicans for 4 weeks showed any histologic evidence of Systemic Candidiasis of endogenous origin. In contrast to Systemic Candidiasis, we observed no significant (P < 0.05) differences in susceptibility among IL-10 KO, IL-4 KO, and wild-type (immunocompetent) mice to orogastric Candidiasis. Our results suggest that IL-10 exerts a negative effect on the early, innate response to acute Systemic Candidiasis; however, in comparison to immunocompetent control (wild-type) mice, neither IL-10 nor IL-4 deficiency enhanced susceptibility to orogastric Candidiasis.
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b cell knockout mice are resistant to mucosal and Systemic Candidiasis of endogenous origin but susceptible to experimental Systemic Candidiasis
The Journal of Infectious Diseases, 1996Co-Authors: Doug R Wagner, Jessica Jonescarson, Andres Vazqueztorres, Thomas F Warner, Edward BalishAbstract:Germfree JHD mice, which lack functional B cells and antibodies, were as resistant to orogastric and disseminated Candidiasis of endogenous origin as were immunocompetent controls. Newborn J HD mice, in contrast to adult mice, were resistant to alimentary tract colonization by Candida albicans for 5-7 days after birth. C. albicans-colonizedJHD mice were more resistant to intravenous challenge with C. albicans and had greater splenocyte proliferative responses to C. albicans antigens than did germfree mice or conventional controls. Thus, innate and acquired T cell-mediated immune responses induced after oral immunization are sufficient to protect J HD mice from mucosal and Systemic Candidiasis of endogenous origin; however, functional B cells may be required to protect mice from a primary intravenous challenge with C. albicans. The role of antibody-mediated immunity (AMI) in host de fense against Candida albicans infections is controversial [1]. Numerous clinical observations suggest that innate and cell mediated immunity (CMI) are more important than AMI in resistance to Candidiasis [2]. Most patients with Candidiasis are neutropenic [3], T cell-deficient, or both; however, most have demonstrable levels of serum antibodies to C. albicans [4]. Patients with congenital defects in AMI (e.g., X-linked agam maglobulinemia and secretory IgA deficiency) but intact CMI are not overly susceptible to mucosal or Systemic Candidiasis [5]. Conversely, recent investigations suggest that antibodies to heat-shock proteins [6] or to specific C. albicans surface antigens [7] play a role in resistance to Systemic Candidiasis. Studies with laboratory animals have not resolved the role of AMI in resistance to Candidiasis. Investigations in mice immunized with C. albicans antigens or treated with high titered immune serum suggest that antibodies are protective [7~ 10] or have no effect [11-13] on murine susceptibility to experimental Systemic Candidiasis. Although immunocompetent mice and an intravenous (iv) challenge route have been used in most studies designed to assess the efficacy of antibody in resistance to Candidiasis, several studies have used congenitally immunodeficient mice (T or B cell-mediated immunity). Athymic mice with de fects in thymus-matured T cells and production of T cell dependent antibodies [14], severe combined immunodefi cient (SCID) mice with defects in T and B cell functions
Kishor M Wasan - One of the best experts on this subject based on the ideXlab platform.
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novel oral amphotericin b formulation ico 010 remains highly effective against murine Systemic Candidiasis following exposure to tropical temperature
Drug Development and Industrial Pharmacy, 2015Co-Authors: Kishor M Wasan, Olena Sivak, Ellen K Wasan, Karen H Bartlett, Pavel GershkovichAbstract:AbstractPurpose: To evaluate the antifungal activity of amphotericin B (AmB) in a mouse model of Systemic Candidiasis following administration of a novel oral AmB formulation (iCo-010) that has been pre-exposed to tropical temperatures.Methods: Amphotericin B (AmB) was prepared as a 5 mg/mL dispersion in a mixture of Peceol, Gelucire 44/14 and VitE-TPGS 2,3 (iCo-010). The formulation was protected from light and incubated in a sealed container at 43 °C for 60 days. Mice infected with Candida albicans were treated with either iCo-010 formulation pre-incubated at 43 °C for 60 days or freshly prepared iCo-010 formulation at doses of 5, 10 and 20 mg/kg once daily for five consecutive days. Single intravenous 5 mg/kg dose of AmBisome® was used as a positive control group. Seven days following the last dose, the kidney, liver, spleen, lung, heart and brain were removed and the number of colony forming units (CFUs) was determined as a measure of tissue fungal load. In addition, the concentration of AmB within ea...
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efficacy of an oral and tropically stable lipid based formulation of amphotericin b ico 010 in an experimental mouse model of Systemic Candidiasis
Lipids in Health and Disease, 2013Co-Authors: Fady Ibrahim, Olena Sivak, Ellen K Wasan, Karen H Bartlett, Kishor M WasanAbstract:Objective An oral lipid based formulation that exhibits tropical stability (iCo-010) was developed to enhance the absorption of orally administered amphotericin B (AmB). iCo-010 has previously shown high efficacy in an acute model of Systemic Candidiasis in rats, directing the focus of this study to be its efficacy in a chronic model of Systemic Candidiasis in mice.
