NDLI: Lipopolysaccharide clearance, bacterial clearance, and systemic inflammatory responses are regulated by cell type-specific functions of TLR4 during sepsis.

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The influence of T cell Ig mucin-3 signaling on central nervous system autoimmune disease is determined by the effector function of the pathogenic T cells.

Lipopolysaccharide clearance, bacterial clearance, and systemic inflammatory responses are regulated by cell type-specific functions of TLR4 during sepsis.

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Lipopolysaccharide clearance, bacterial clearance, and systemic inflammatory responses are regulated by cell type-specific functions of TLR4 during sepsis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Loughran, Patricia Billiar, Timothy R. Scott, Melanie J. Hackam, David Gibson, Gregory Sodhi, Chhinder Deng, Meihong Watkins, Simon
Description	Country affiliation: United States Author Affiliation: Deng M ( Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.)
Abstract	The morbidity associated with bacterial sepsis is the result of host immune responses to pathogens, which are dependent on pathogen recognition by pattern recognition receptors, such as TLR4. TLR4 is expressed on a range of cell types, yet the mechanisms by which cell-specific functions of TLR4 lead to an integrated sepsis response are poorly understood. To address this, we generated mice in which TLR4 was specifically deleted from myeloid cells (LysMTLR4KO) or hepatocytes (HCTLR4KO) and then determined survival, bacterial counts, host inflammatory responses, and organ injury in a model of cecal ligation and puncture (CLP), with or without antibiotics. LysM-TLR4 was required for phagocytosis and efficient bacterial clearance in the absence of antibiotics. Survival, the magnitude of the systemic and local inflammatory responses, and liver damage were associated with bacterial levels. HCTLR4 was required for efficient LPS clearance from the circulation, and deletion of HCTLR4 was associated with enhanced macrophage phagocytosis, lower bacterial levels, and improved survival in CLP without antibiotics. Antibiotic administration during CLP revealed an important role for hepatocyte LPS clearance in limiting sepsis-induced inflammation and organ injury. Our work defines cell type-selective roles for TLR4 in coordinating complex immune responses to bacterial sepsis and suggests that future strategies for modulating microbial molecule recognition should account for varying roles of pattern recognition receptors in multiple cell populations.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1300496
Journal	The Journal of Immunology
Issue Number	10
Volume Number	190
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2013-05-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Bacterial Load Immunology Inflammation Lipopolysaccharides Metabolism Toll-like Receptor 4 Animals Cecum Surgery Cells, Cultured Hepatocytes Cytology Interleukin-6 Blood Liver Injuries Microbiology Macrophages Mice Mice, Inbred C57bl Mice, Knockout Myeloid Cells Neutrophils Phagocytosis Sepsis Mortality Deficiency Genetics Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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