Tissue Damage Signaling Is a Prerequisite for Protective Neutrophil Recruitment to Microbial Infection in Zebrafish

Immunity
Cong Huang, Philipp Niethammer

Abstract

Tissue damage and infection are deemed likewise triggers of innate immune responses. But whereas neutrophil responses to microbes are generally protective, neutrophil recruitment into damaged tissues without infection is deleterious. Why neutrophils respond to tissue damage and not just to microbes is unknown. Is it a flaw of the innate immune system that persists because evolution did not select against it, or does it provide a selective advantage? Here we dissect the contribution of tissue damage signaling to antimicrobial immune responses in a live vertebrate. By intravital imaging of zebrafish larvae, a powerful model for innate immunity, we show that prevention of tissue damage signaling upon microbial ear infection abrogates leukocyte chemotaxis and reduces animal survival, at least in part, through suppression of cytosolic phospholipase A2 (cPla2), which integrates tissue damage- and microbe-derived cues. Thus, microbial cues are insufficient, and damage signaling is essential for antimicrobial neutrophil responses in zebrafish.

Citations

Jun 4, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Oliver Gordon, Caetano Reis E Sousa
Sep 5, 2019·Nature·Sarah R Walmsley
Aug 25, 2019·Cells·Gabriel Forn-CuníMonica Varela
Sep 29, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wei ShiJian-Zhong Shao
Feb 13, 2020·Npj Regenerative Medicine·Celia Herrera-RinconMichael Levin
Jul 15, 2020·Cellular and Molecular Life Sciences : CMLS·Agnes Ulfig, Lars I Leichert
Sep 2, 2020·Nature Cell Biology·Anushka KatikaneniPhilipp Niethammer
May 10, 2019·Development·Hanna ReuterFlorenci Serras
Jan 12, 2019·Scientific Reports·Michelina StoddardPhilipp Niethammer
Sep 27, 2019·Frontiers in Immunology·Caitlin C Murdoch, John F Rawls
Nov 14, 2020·Anesthesia and Analgesia·Catharina Conrad, Holger K Eltzschig
Feb 4, 2021·Npj Regenerative Medicine·Celia Herrera-RinconMichael Levin
May 18, 2021·Frontiers in Cell and Developmental Biology·Paco López-CuevasPaul Martin
May 29, 2021·The Journal of Cell Biology·Ruth A HouserightAnna Huttenlocher
Jul 3, 2021·Annual Review of Cell and Developmental Biology·Philipp Niethammer

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