Macrophage-derived LTB4promotes abscess formation and clearance of Staphylococcus aureus skin infection in mice

Stephanie L. Brandt, Nathan Klopfenstein, Soujuan Wang, Seth Winfree, Brian P. McCarthy, Paul Territo, Lloyd Miller, C. Henrique Serezani

Research output: Contribution to journalArticle

Abstract

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 LTB4enhances antimicrobial effector functions in vitro, whether prompt LTB4production is required for bacterial clearance and development of an inflammatory milieu necessary for abscess formation to restrain pathogen dissemination is unknown. We found that LTB4is 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 LTB4synergizes with antibiotics to eliminate MRSA potently. Here, we uncovered a heretofore unknown role of macrophage-derived LTB4in orchestrating the chemoattractant gradient required for abscess formation, while amplifying antimicrobial effector functions.

Original languageEnglish (US)
Article numbere1007244
JournalPLoS Pathogens
Volume14
Issue number8
DOIs
StatePublished - Aug 1 2018
Externally publishedYes

Fingerprint

Abscess
Staphylococcus aureus
Macrophages
Phagocytes
Skin
Infection
Neutrophils
Chemotactic Factors
Chemotaxis
Methicillin-Resistant Staphylococcus aureus
Monocytes
Arachidonate 5-Lipoxygenase
Leukotriene B4
Ointments
G-Protein-Coupled Receptors
Chemokines
Innate Immunity
Reactive Oxygen Species
Anti-Bacterial Agents
Lipids

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Brandt, S. L., Klopfenstein, N., Wang, S., Winfree, S., McCarthy, B. P., Territo, P., ... Serezani, C. H. (2018). Macrophage-derived LTB4promotes abscess formation and clearance of Staphylococcus aureus skin infection in mice. PLoS Pathogens, 14(8), [e1007244]. https://doi.org/10.1371/journal.ppat.1007244

Macrophage-derived LTB4promotes abscess formation and clearance of Staphylococcus aureus skin infection in mice. / Brandt, Stephanie L.; Klopfenstein, Nathan; Wang, Soujuan; Winfree, Seth; McCarthy, Brian P.; Territo, Paul; Miller, Lloyd; Serezani, C. Henrique.

In: PLoS Pathogens, Vol. 14, No. 8, e1007244, 01.08.2018.

Research output: Contribution to journalArticle

Brandt, SL, Klopfenstein, N, Wang, S, Winfree, S, McCarthy, BP, Territo, P, Miller, L & Serezani, CH 2018, 'Macrophage-derived LTB4promotes abscess formation and clearance of Staphylococcus aureus skin infection in mice', PLoS Pathogens, vol. 14, no. 8, e1007244. https://doi.org/10.1371/journal.ppat.1007244
Brandt, Stephanie L. ; Klopfenstein, Nathan ; Wang, Soujuan ; Winfree, Seth ; McCarthy, Brian P. ; Territo, Paul ; Miller, Lloyd ; Serezani, C. Henrique. / Macrophage-derived LTB4promotes abscess formation and clearance of Staphylococcus aureus skin infection in mice. In: PLoS Pathogens. 2018 ; Vol. 14, No. 8.
@article{92be27cc697e4db2b6128c22cd94555d,
title = "Macrophage-derived LTB4promotes abscess formation and clearance of Staphylococcus aureus skin infection in mice",
abstract = "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 LTB4enhances antimicrobial effector functions in vitro, whether prompt LTB4production is required for bacterial clearance and development of an inflammatory milieu necessary for abscess formation to restrain pathogen dissemination is unknown. We found that LTB4is 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 LTB4synergizes with antibiotics to eliminate MRSA potently. Here, we uncovered a heretofore unknown role of macrophage-derived LTB4in orchestrating the chemoattractant gradient required for abscess formation, while amplifying antimicrobial effector functions.",
author = "Brandt, {Stephanie L.} and Nathan Klopfenstein and Soujuan Wang and Seth Winfree and McCarthy, {Brian P.} and Paul Territo and Lloyd Miller and Serezani, {C. Henrique}",
year = "2018",
month = "8",
day = "1",
doi = "10.1371/journal.ppat.1007244",
language = "English (US)",
volume = "14",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "8",

}

TY - JOUR

T1 - Macrophage-derived LTB4promotes abscess formation and clearance of Staphylococcus aureus skin infection in mice

AU - Brandt, Stephanie L.

AU - Klopfenstein, Nathan

AU - Wang, Soujuan

AU - Winfree, Seth

AU - McCarthy, Brian P.

AU - Territo, Paul

AU - Miller, Lloyd

AU - Serezani, C. Henrique

PY - 2018/8/1

Y1 - 2018/8/1

N2 - 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 LTB4enhances antimicrobial effector functions in vitro, whether prompt LTB4production is required for bacterial clearance and development of an inflammatory milieu necessary for abscess formation to restrain pathogen dissemination is unknown. We found that LTB4is 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 LTB4synergizes with antibiotics to eliminate MRSA potently. Here, we uncovered a heretofore unknown role of macrophage-derived LTB4in orchestrating the chemoattractant gradient required for abscess formation, while amplifying antimicrobial effector functions.

AB - 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 LTB4enhances antimicrobial effector functions in vitro, whether prompt LTB4production is required for bacterial clearance and development of an inflammatory milieu necessary for abscess formation to restrain pathogen dissemination is unknown. We found that LTB4is 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 LTB4synergizes with antibiotics to eliminate MRSA potently. Here, we uncovered a heretofore unknown role of macrophage-derived LTB4in orchestrating the chemoattractant gradient required for abscess formation, while amplifying antimicrobial effector functions.

UR - http://www.scopus.com/inward/record.url?scp=85053077129&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053077129&partnerID=8YFLogxK

U2 - 10.1371/journal.ppat.1007244

DO - 10.1371/journal.ppat.1007244

M3 - Article

VL - 14

JO - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 8

M1 - e1007244

ER -