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© 2023, Bhosle et al. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Neutrophils are essential for host defense against Staphylococcus aureus (S. aureus). The neuro-repellent, SLIT2, potently inhibits neutrophil chemotaxis, and might, therefore, be expected to impair antibacterial responses. We report here that, unexpectedly, neutrophils exposed to the N-terminal SLIT2 (N-SLIT2) fragment kill extracellular S. aureus more efficiently. N-SLIT2 amplifies reactive oxygen species production in response to the bacteria by activating p38 mitogen-activated protein kinase that in turn phosphorylates NCF1, an essential subunit of the NADPH oxidase complex. N-SLIT2 also enhances the exocytosis of neutrophil secondary granules. In a murine model of S. aureus skin and soft tissue infection (SSTI), local SLIT2 levels fall initially but increase subsequently, peaking at 3 days after infection. Of note, the neutralization of endogenous SLIT2 worsens SSTI. Temporal fluctuations in local SLIT2 levels may promote neutrophil recruitment and retention at the infection site and hasten bacterial clearance by augmenting neutrophil oxidative burst and degranulation. Collectively, these actions of SLIT2 coordinate innate immune responses to limit susceptibility to S. aureus.

Details

Title
The chemorepellent, SLIT2, bolsters innate immunity against Staphylococcus aureus
Author
Bhosle, Vikrant K; Sun Chunxiang; Patel Sajedabanu; Ho Tse Wing Winnie; Westman, Johannes; Ammendolia, Dustin A; Langari, Fatemeh Mirshafiei; Fine, Noah; Toepfner Nicole; Li, Zhubing; Sharma Manraj; Glogauer Judah; Capurro, Mariana I; Jones, Nicola L; Maynes, Jason T; Lee, Warren L; Glogauer, Michael; Grinstein, Sergio; Robinson, Lisa A
University/institution
U.S. National Institutes of Health/National Library of Medicine
Publication year
2023
Publication date
2023
Publisher
eLife Sciences Publications Ltd.
e-ISSN
2050084X
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2884578408
Copyright
© 2023, Bhosle et al. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.