The Experts below are selected from a list of 20067 Experts worldwide ranked by ideXlab platform
Kojiunn Liu - One of the best experts on this subject based on the ideXlab platform.
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human placental msc secreted il 1β enhances neutrophil bactericidal functions during hypervirulent Klebsiella Infection
Cell Reports, 2020Co-Authors: Litzu Wang, Hsiuhuan Wang, H C Chiang, Liyueh Huang, Shengkang Chiu, Kristopher L Siu, Kojiunn LiuAbstract:Summary Hypervirulent Klebsiella pneumoniae (hvKP) causes severe Infections even in healthy individuals by escaping surveillance and killing from polymorphonuclear neutrophils (PMNs), the first-line leukocytes in bacterial Infections; moreover, the emergence of multidrug-resistant strains further limits treatment options. We therefore assess whether multilineage mesenchymal stem cells (MSCs), best known for immunomodulation toward T cells, could be therapeutic for highly virulent bacterial Infections via modulation of PMNs. We find that both bone marrow MSCs and placental MSCs (PMSCs) preserve in vitro PMN survival, but only PMSCs significantly enhance multiple PMN bactericidal functions, including phagocytosis, through secretion of interleukin-1β (IL-1β). PMSC treatment of hvKP-infected mice suppresses T and natural killer (NK) cell responses as expected but can preferentially recruit PMNs and enhance antibacterial functions to allow for disease survival; IL-1β knockdown in PMSCs significantly decreases hvKP clearance, worsening survival and resulting in 100% lethality. Our data strongly implicate the possible use of PMSCs for Infections of PMN-resistant hvKP strains.
Samithamby Jeyaseelan - One of the best experts on this subject based on the ideXlab platform.
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intrapulmonary administration of leukotriene b 4 augments neutrophil accumulation and responses in the lung to Klebsiella Infection in cxcl1 knockout mice
Journal of Immunology, 2012Co-Authors: Sanjay Batra, Gayathriy Balamayooran, Samithamby JeyaseelanAbstract:In prior studies, we demonstrated that 1) CXCL1/KC is essential for NF-κB and MAPK activation and expression of CXCL2/MIP-2 and CXCL5/LPS-induced CXC chemokine in Klebsiella-infected lungs, and 2) CXCL1 derived from hematopoietic and resident cells contributes to host immunity against Klebsiella. However, the role of CXCL1 in mediating neutrophil leukotriene B4 (LTB4), reactive oxygen species (ROS), and reactive nitrogen species (RNS) production is unclear, as is the contribution of these factors to host immunity. In this study, we investigated 1) the role of CXCL1 in LTB4, NADPH oxidase, and inducible NO synthase (iNOS) expression in lungs and neutrophils, and 2) whether LTB4 postInfection reverses innate immune defects in CXCL1−/− mice via regulation of NADPH oxidase and iNOS. Our results demonstrate reduced neutrophil influx, attenuated LTB4 levels, and decreased ROS and iNOS production in the lungs of CXCL1−/− mice after Klebsiella pneumoniae Infection. Using neutrophil depletion and repletion, we found that neutrophils are the predominant source of pulmonary LTB4 after Infection. To treat immune defects in CXCL1−/− mice, we intrapulmonarily administered LTB4. PostInfection, LTB4 treatment reversed immune defects in CXCL1−/− mice and improved survival, neutrophil recruitment, cytokine/chemokine expression, NF-κB/MAPK activation, and ROS/RNS production. LTB4 also enhanced myeloperoxidase, H2O2, RNS production, and bacterial killing in K. pneumoniae-infected CXCL1−/− neutrophils. These novel results uncover important roles for CXCL1 in generating ROS and RNS in neutrophils and in regulating host immunity against K. pneumoniae Infection. Our findings suggest that LTB4 could be used to correct defects in neutrophil recruitment and function in individuals lacking or expressing malfunctional CXCL1.
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cxcl1 regulates pulmonary host defense to Klebsiella Infection via cxcl2 cxcl5 nf κb and mapks
Journal of Immunology, 2010Co-Authors: Sanjay Batra, Samithamby Jeyaseelan, Sergio A Lira, Jay K. KollsAbstract:Pulmonary bacterial Infections are a leading cause of death. Since the introduction of antibiotics, multidrug-resistant Klebsiella pneumoniae became an escalating threat. Therefore, development of methods to augment antibacterial defense is warranted. Neutrophil recruitment is critical to clear bacteria, and neutrophil migration in the lung requires the production of ELR + CXC chemokines. Although lung-specific CXCL1/keratinocyte cell-derived chemokine (KC) transgene expression causes neutrophil-mediated clearance of K. pneumoniae , the mechanisms underlying KC-mediated host defense against K. pneumoniae have not been explored. In this study, we delineated the host defense functions of KC during pulmonary K. pneumoniae Infection using KC −/− mice. Our findings demonstrate that KC is important for expression of CXCL2/MIP-2 and CXCL5/LPS-induced CXC chemokine, and activation of NF-κB and MAPKs in the lung. Furthermore, KC derived from both hematopoietic and resident cells contributes to host defense against K. pneumoniae . Neutrophil depletion in mice before K. pneumoniae Infection reveals no differences in the production of MIP-2 and LPS-induced CXC chemokine or activation of NF-κB and MAPKs in the lung. Using murine bone marrow-derived and alveolar macrophages, we confirmed KC-mediated upregulation of MIP-2 and activation of NF-κB and MAPKs on K. pneumoniae Infection. Moreover, neutralizing KC in bone marrow-derived macrophages before K. pneumoniae challenge decreases bacteria-induced production of KC and MIP-2, and activation of NF-κB and MAPKs. These findings reveal the importance of KC produced by hematopoietic and resident cells in regulating pulmonary host defense against a bacterial pathogen via the activation of transcription factors and MAPKs, as well as the expression of cell adhesion molecules and other neutrophil chemoattractants.
Kristopher L Siu - One of the best experts on this subject based on the ideXlab platform.
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human placental msc secreted il 1β enhances neutrophil bactericidal functions during hypervirulent Klebsiella Infection
Cell Reports, 2020Co-Authors: Litzu Wang, Hsiuhuan Wang, H C Chiang, Liyueh Huang, Shengkang Chiu, Kristopher L Siu, Kojiunn LiuAbstract:Summary Hypervirulent Klebsiella pneumoniae (hvKP) causes severe Infections even in healthy individuals by escaping surveillance and killing from polymorphonuclear neutrophils (PMNs), the first-line leukocytes in bacterial Infections; moreover, the emergence of multidrug-resistant strains further limits treatment options. We therefore assess whether multilineage mesenchymal stem cells (MSCs), best known for immunomodulation toward T cells, could be therapeutic for highly virulent bacterial Infections via modulation of PMNs. We find that both bone marrow MSCs and placental MSCs (PMSCs) preserve in vitro PMN survival, but only PMSCs significantly enhance multiple PMN bactericidal functions, including phagocytosis, through secretion of interleukin-1β (IL-1β). PMSC treatment of hvKP-infected mice suppresses T and natural killer (NK) cell responses as expected but can preferentially recruit PMNs and enhance antibacterial functions to allow for disease survival; IL-1β knockdown in PMSCs significantly decreases hvKP clearance, worsening survival and resulting in 100% lethality. Our data strongly implicate the possible use of PMSCs for Infections of PMN-resistant hvKP strains.
Jay K. Kolls - One of the best experts on this subject based on the ideXlab platform.
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cxcl1 regulates pulmonary host defense to Klebsiella Infection via cxcl2 cxcl5 nf κb and mapks
Journal of Immunology, 2010Co-Authors: Sanjay Batra, Samithamby Jeyaseelan, Sergio A Lira, Jay K. KollsAbstract:Pulmonary bacterial Infections are a leading cause of death. Since the introduction of antibiotics, multidrug-resistant Klebsiella pneumoniae became an escalating threat. Therefore, development of methods to augment antibacterial defense is warranted. Neutrophil recruitment is critical to clear bacteria, and neutrophil migration in the lung requires the production of ELR + CXC chemokines. Although lung-specific CXCL1/keratinocyte cell-derived chemokine (KC) transgene expression causes neutrophil-mediated clearance of K. pneumoniae , the mechanisms underlying KC-mediated host defense against K. pneumoniae have not been explored. In this study, we delineated the host defense functions of KC during pulmonary K. pneumoniae Infection using KC −/− mice. Our findings demonstrate that KC is important for expression of CXCL2/MIP-2 and CXCL5/LPS-induced CXC chemokine, and activation of NF-κB and MAPKs in the lung. Furthermore, KC derived from both hematopoietic and resident cells contributes to host defense against K. pneumoniae . Neutrophil depletion in mice before K. pneumoniae Infection reveals no differences in the production of MIP-2 and LPS-induced CXC chemokine or activation of NF-κB and MAPKs in the lung. Using murine bone marrow-derived and alveolar macrophages, we confirmed KC-mediated upregulation of MIP-2 and activation of NF-κB and MAPKs on K. pneumoniae Infection. Moreover, neutralizing KC in bone marrow-derived macrophages before K. pneumoniae challenge decreases bacteria-induced production of KC and MIP-2, and activation of NF-κB and MAPKs. These findings reveal the importance of KC produced by hematopoietic and resident cells in regulating pulmonary host defense against a bacterial pathogen via the activation of transcription factors and MAPKs, as well as the expression of cell adhesion molecules and other neutrophil chemoattractants.
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lipocalin 2 is required for pulmonary host defense against Klebsiella Infection
Journal of Immunology, 2009Co-Authors: Yvonne R Chan, Derek A Pociask, Mingquan Zheng, Matthew C. Clifton, Roland K. Strong, Thorsten Berger, Timothy A. Mietzner, Jay K. KollsAbstract:Antimicrobial proteins comprise a significant component of the acute innate immune response to Infection. They are induced by pattern recognition receptors as well as by cytokines of the innate and adaptive immune pathways and play important roles in Infection control and immunomodulatory homeostasis. Lipocalin 2 (siderocalin, NGAL, 24p3), a siderophore-binding antimicrobial protein, is critical for control of systemic Infection with Escherichia coli; however, its role in mucosal immunity in the respiratory tract is unknown. In this study, we found that lipocalin 2 is rapidly and robustly induced by Klebsiella pneumoniae Infection and is TLR4 dependent. IL-1β and IL-17 also individually induce lipocalin 2. Mucosal administration of IL-1β alone could reconstitute the lipocalin 2 deficiency in TLR4 knockout animals and rescue them from Infection. Lipocalin 2-deficient animals have impaired lung bacterial clearance in this model and mucosal reconstitution of lipocalin 2 protein in these animals resulted in rescue of this phenotype. We conclude that lipocalin 2 is a crucial component of mucosal immune defense against pulmonary Infection with K. pneumoniae.
Pizanis Charles - One of the best experts on this subject based on the ideXlab platform.
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Clinical vignette: Leaching liver lesions: a case of invasive Klebsiella pneumoniae liver abscess syndrome
2014Co-Authors: Liaboe Lauren, Cutrufello Nicholas, Huelskamp Stephen, Carson Trechelle, Ronan Theresa, Pizanis CharlesAbstract:Presented at American College of Physicians New Mexico Chapter Scientific Meeting, 11/07/2014, Albuquerque, NM.Klebsiella pneumoniae liver abscesses are becoming more prevalent in the United States and have the ability to spread to several sites via septic embolization. 8-15% of patients have Infections at other anatomical sites which is considered invasive K. pneumoniae liver abscess syndrome (IKPLAS). An otherwise healthy 42-year-old Vietnamese man who immigrated to the United States six years prior presented to the emergency department with a nine-day history of back pain. The patient reported his pain worsened acutely just prior to presentation when lifting a heavy object. He also described numbness of the left leg. At presentation, the patient was septic. Because of this, a MRI of the lumbar spine was obtained which demonstrated multiple paraspinal and gluteal region abscesses. A chest CT demonstrated a 2cm right hepatic lobe hypoattenuating lesion suggestive of an abscess as well as multiple pulmonary nodules with peripheral and upper lobe predominance. Blood cultures drawn prior to initiation of antibiotics grew out Klebsiella pneumoniae. Given the patient’s ethnic background and the organism isolated, the liver lesion was suspected as the primary abscess, with hematogenous dissemination to the lungs, paraspinal and gluteal regions, this being consistent with IKPLAS. The patient underwent drainage of the piriformis muscle abscess which also yielded K. pneumoniae. When cultures returned positive for K. pneumoniae, the antibiotic regimen was narrowed to ceftriaxone based on organism susceptibility. Despite appropriate antibiotic therapy, he went on to develop further abscesses as well osteomyelitis of the L1 and L2 vertebrae. He underwent subsequent abscess drainage after which the patient defervesced and his back pain improved. The patient was eventually discharged on ceftriaxone 2gm every 12 hours and received a total of eight weeks of antibiotics. Invasive Klebsiella pneumoniae liver abscesses syndrome (IKPLAS) is a rare clinical disease entity defined as a liver abscess and disseminated Klebsiella Infection. It is often seen in patients of Asian descent and is increasing in prevalence within the United States. IKPLAS is associated with a high degree of morbidity and mortality. It should be considered in septic patients who are found to have liver abscesses and are of Asian descent
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Clinical vignette: Leaching liver lesions: a case of invasive Klebsiella pneumoniae liver abscess syndrome
UNM Digital Repository, 2014Co-Authors: Liaboe Lauren, Cutrufello Nicholas, Huelskamp Stephen, Carson Trechelle, Ronan Theresa, Pizanis CharlesAbstract:Klebsiella pneumoniae liver abscesses are becoming more prevalent in the United States and have the ability to spread to several sites via septic embolization. 8-15% of patients have Infections at other anatomical sites which is considered invasive K. pneumoniae liver abscess syndrome (IKPLAS). An otherwise healthy 42-year-old Vietnamese man who immigrated to the United States six years prior presented to the emergency department with a nine-day history of back pain. The patient reported his pain worsened acutely just prior to presentation when lifting a heavy object. He also described numbness of the left leg. At presentation, the patient was septic. Because of this, a MRI of the lumbar spine was obtained which demonstrated multiple paraspinal and gluteal region abscesses. A chest CT demonstrated a 2cm right hepatic lobe hypoattenuating lesion suggestive of an abscess as well as multiple pulmonary nodules with peripheral and upper lobe predominance. Blood cultures drawn prior to initiation of antibiotics grew out Klebsiella pneumoniae. Given the patients ethnic background and the organism isolated, the liver lesion was suspected as the primary abscess, with hematogenous dissemination to the lungs, paraspinal and gluteal regions, this being consistent with IKPLAS. The patient underwent drainage of the piriformis muscle abscess which also yielded K. pneumoniae. When cultures returned positive for K. pneumoniae, the antibiotic regimen was narrowed to ceftriaxone based on organism susceptibility. Despite appropriate antibiotic therapy, he went on to develop further abscesses as well osteomyelitis of the L1 and L2 vertebrae. He underwent subsequent abscess drainage after which the patient defervesced and his back pain improved. The patient was eventually discharged on ceftriaxone 2gm every 12 hours and received a total of eight weeks of antibiotics. Invasive Klebsiella pneumoniae liver abscesses syndrome (IKPLAS) is a rare clinical disease entity defined as a liver abscess and disseminated Klebsiella Infection. It is often seen in patients of Asian descent and is increasing in prevalence within the United States. IKPLAS is associated with a high degree of morbidity and mortality. It should be considered in septic patients who are found to have liver abscesses and are of Asian descent.\u2