Immunomodulation of Host Chitinase 3-Like 1 During a Mammary Pathogenic Escherichia coli Infection.

Koen Breyne,Jonas Steenbrugge,Chun Geun Lee,Wolfram Petzl,Pierre Germon,Jack A Elias,Evelyne Meyer,David G E Smith,Kristel Demeyere

doi:10.3389/fimmu.2018.01143

Abstract

Chitin is a N-acetyl-d-glucosamine biopolymer that can be recognized by chitin-binding proteins. Although mammals lack chitin synthase, they induce proteins responsible for detecting chitin in response to bacterial infections. Our aim was to investigate whether chitinase 3-like 1 (CHI3L1) has a potential role in the innate immunity of the Escherichia coli (E. coli) infected mammary gland. CHI3L1 protein was found to be secreted in whey of naturally coliform-affected quarters compared to whey samples isolated from healthy udders. In addition, gene expression of CHI3L1 was confirmed in udder tissue of cows experimentally infected with a mammary pathogenic E. coli (MPEC) strain. Despite the known anatomical differences, the bovine udders’ innate immune response was mimicked by applying an experimental mouse model using MPEC or non-MPEC isolates. The effect of CHI3L1 expression in the murine mammary gland in response to coliform bacteria was investigated through the use of CHI3L1−/− mice as well as through treatment with either a pan-caspase inhibitor or chitin particles in wild-type mice. The local induction of CHI3L1 postinfection with different E. coli strains was demonstrated to be independent of both bacterial growth and mammary interleukin (IL)-8 levels. Indeed, CHI3L1 emerged as a regulator impacting on the transcytosis of Ly6G-positive cells from the interstitial space into the alveolar lumen of the mammary tissue. Furthermore, CHI3L1 was found to be upstream regulated by caspase activity and had a major downstream effect on the local pro-inflammatory cytokine profile, including IL-1beta, IL-6, and RANTES/CCL5. In conclusion, CHI3L1 was demonstrated to play a key role in the cytokine and caspase signaling during E. coli triggered inflammation of the mammary gland.

Highlights

Chitin is a prominent polymer present within the cuticle of arthropods, plays a crucial part of cephalopods and the cell wall of fungi, but is absent in mammals [1,2,3]
chitinase 3-like 1 (CHI3L1) Signaling in Coliform Mastitis hydrolase (GH18) family, which can be divided into two subfa milies: chitinase-like proteins (CLPs), which bind chitin but do not possess chitinolytic activity and chitinases, which bind chitin and subsequently hydrolyze their substrate [4]
Whey obtained from milk samples of dairy cows diagnosed with coliform mastitis (n = 7) were analyzed for the presence of CHI3L1

Summary

Introduction

Chitin is a prominent polymer present within the cuticle of arthropods, plays a crucial part of cephalopods and the cell wall of fungi, but is absent in mammals [1,2,3]. Members of the GH18 family detect chitin in pathogenic organisms and trigger expression and activation of mammalian chitinase(-like) proteins, which have been implicated in the inflammatory response against these organisms [7]. In response to lung infections or bone marrow-derived macrophages, chitinase 3-like 1 (CHI3L1) participates in the immune defense and bacterial clearance through inhibition of caspase-1-dependent macrophage pyroptosis [15, 16]. These observations imply that mammalian chitinase(-like) proteins are likely to play a key role of the hosts’ (innate) immune response [17, 18]. The underlying molecular mechanism in which these proteins are involved remains poorly understood

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