Cathepsin L promotes secretory IgA response by participating in antigen presentation pathways during Mycoplasma Hyopneumoniae infection.

Ning Zhang,Jiahe Li,Yu Kuang,Wenxue Wu,Tong Wu,Bao Yin,Peng Gao,Jinxiang Li,Paulo Lee Ho

doi:10.1371/journal.pone.0215408

Abstract

Cathepsin L (CTSL) has been proved to help contain leishmaniasis and mycoplasma infection in mice by supporting cellular immune responses, but the regulatory functions of CTSL on mucosal immune responses haven’t been tested and remain undefined. Here, we investigated the effects of CTSL on SIgA responses and invariant chain (Ii) degradations in the co-cultured swine dendritic cells (DCs) and B cells system in vitro. When the cells system were transfected with vector CTSL-GFP or incubated with recombinant CTSL (rCTSL) before they were infected with Mycoplasma hyopneumoniae (M.hp), SIgA significantly increased and Ii chain was degraded into smaller intermediates, while SIgA decreased when CTSL was knockdown or inhibited with E64. To confirm the SIgA responses promoted by CTSL contribute to the resistance to mycoplasma pneumonia, pigs injected with rCTSL before they were challenged with M.hp, showed milder clinical symptoms and histopathological damage of lungs, less mycoplasma burden together with higher secretion of SIgA, percentages of CD4+ T cells and level of MHC II molecules comparing with the group without rCTSL. Collectively, these results suggested that rCTSL could provide effective protection for piglets against mycoplasma pneumonia by enhancing M.hp-specific mucosal immune responses through its role in antigen presentation by processing the invariant chain.

Highlights

Mucosal surfaces of the respiratory tract and gastrointestinal tract are the first line of defense to prevent the infection of pathogens and clear the evaded microorganism by excreting active components including secretory immunoglobulin A (SIgA) [1, 2]
We investigated the preventive effects of recombinant Cathepsin L (CTSL) on mycoplasma pneumonia of swine which is the most approximate model to humans [31, 32], and the effects of rCTSL and native CTSL on SIgA responses and invariant chain (Ii) degradations in the co-cultured dendritic cells (DCs) and B cells model in vitro
The concentrations of CTSL in DCs and macrophages in various tissues of the pigs were detected by sandwich ELISA in order to select the ideal type of antigen presentation cells (APCs)

Summary

Introduction

Mucosal surfaces of the respiratory tract and gastrointestinal tract are the first line of defense to prevent the infection of pathogens and clear the evaded microorganism by excreting active components including secretory immunoglobulin A (SIgA) [1, 2]. Experimental evidence showed that SIgA response provides effective protection especially for the cases of chronic mucosal infections and reinfections of many bacteria, virus, parasites and fungi [3,4,5,6]. Cathepsin L promotes SIgA in mycoplasma-infected swine. Mycoplasma, unlike virus or bacteria, leads infection by firmly adhering to respiratory epithelial cells. Mucosal immunity instead of systemic immunity plays a key role during infection [7]. SIgA is the first sign of mycoplasma infection which raises the strategy considerations about the induction of SIgA by vaccination [8, 9]

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Discussion

Conclusion