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Macrophage-derived LTB4 promotes abscess formation and clearance of Staphylococcus aureus skin infection in mice.

08:00 EDT 13th August 2018 | BioPortfolio

Summary of "Macrophage-derived LTB4 promotes abscess formation and clearance of Staphylococcus aureus skin infection in mice."

The early events that shape the innate immune response to restrain pathogens during skin infections remain elusive. Methicillin-resistant Staphylococcus aureus (MRSA) infection engages phagocyte chemotaxis, abscess formation, and microbial clearance. Upon infection, neutrophils and monocytes find a gradient of chemoattractants that influence both phagocyte direction and microbial clearance. The bioactive lipid leukotriene B4 (LTB4) is quickly (seconds to minutes) produced by 5-lipoxygenase (5-LO) and signals through the G protein-coupled receptors LTB4R1 (BLT1) or BLT2 in phagocytes and structural cells. Although it is known that LTB4 enhances antimicrobial effector functions in vitro, whether prompt LTB4 production is required for bacterial clearance and development of an inflammatory milieu necessary for abscess formation to restrain pathogen dissemination is unknown. We found that LTB4 is produced in areas near the abscess and BLT1 deficient mice are unable to form an abscess, elicit neutrophil chemotaxis, generation of neutrophil and monocyte chemokines, as well as reactive oxygen species-dependent bacterial clearance. We also found that an ointment containing LTB4 synergizes with antibiotics to eliminate MRSA potently. Here, we uncovered a heretofore unknown role of macrophage-derived LTB4 in orchestrating the chemoattractant gradient required for abscess formation, while amplifying antimicrobial effector functions.

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Journal Details

This article was published in the following journal.

Name: PLoS pathogens
ISSN: 1553-7374
Pages: e1007244

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Medical and Biotech [MESH] Definitions

A species of STAPHYLOCOCCUS similar to STAPHYLOCOCCUS HAEMOLYTICUS, but containing different esterases. The subspecies Staphylococcus hominis novobiosepticus is highly virulent and novobiocin resistant.

A COAGULASE-negative species of STAPHYLOCOCCUS found on the skin and MUCOUS MEMBRANE of warm-blooded animals. Similar to STAPHYLOCOCCUS EPIDERMIDIS and STAPHYLOCOCCUS HAEMOLYTICUS, it is a nosocomial pathogen in NICU settings. Subspecies include generally antibiotic susceptible and BIOFILM negative capitis and antibiotic resistant and biofilm positive urealyticus isolates.

A powerful flexor of the thigh at the hip joint (psoas major) and a weak flexor of the trunk and lumbar spinal column (psoas minor). Psoas is derived from the Greek "psoa", the plural meaning "muscles of the loin". It is a common site of infection manifesting as abscess (PSOAS ABSCESS). The psoas muscles and their fibers are also used frequently in experiments in muscle physiology.

The process of altering the morphology and functional activity of macrophages so that they become avidly phagocytic. It is initiated by lymphokines, such as the macrophage activation factor (MAF) and the macrophage migration-inhibitory factor (MMIF), immune complexes, C3b, and various peptides, polysaccharides, and immunologic adjuvants.

Viruses whose host is Staphylococcus.

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