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

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.

Genomic Variability and Post-translational Protein Processing Enhance the Immune Evasion of Mycoplasma hyopneumoniae and Its Interaction With the Porcine Immune System

“…In order to strengthen immune responses, certain adjuvants can be used as a component in the vaccine formula. What's more, the use of appropriate pharmacotherapy to improve the host immunity, especially mucosal immunity, is another attractive treatment method ( 96 ), which can be regarded as an assistant method for vaccine development. Reducing the adverse effects of immune evasion and enhancing host immunity are critical directions for vaccine development and medicine research and unraveling the immune evasion mechanisms and pathogenesis of Mhp will pave the way for the development of new therapeutics for MPS.…”

“…The mucosal surface of the respiratory tract is the first defense line to prevent pathogens infection and eliminate microorganisms (bacteria, virus, parasites, and fungi) or foreign bodies by producing active components like SIgA ( 94 , 95 ). On the other hand, mucosal immunity is an important sign of Mhp infection and could be improved by cathepsin L, which should be considered into the medication development ( 96 ).…”

Toll-Like Receptor 2 (TLR2) and TLR4 Mediate the IgA Immune Response Induced by Mycoplasma hyopneumoniae

“…hyopneumoniae, suggesting that the coculture of primary porcine DC and B cells can effectively produce IgA under the stimulation of M. hyopneumoniae (34) and indicating that the DC/B cell culture in vitro could be a good model for studying the IgA response to M. hyopneumoniae.…”

Cathepsins in Bacteria-Macrophage Interaction: Defenders or Victims of Circumstance?

“…Treatment of animals with rCts L before challenge with M. hyopneumoniae resulted in milder clinical symptoms, little histopathological damage of lungs and lower mycoplasma burden accompanied by higher secretion of sIgA, higher percentages of CD4 + T cells and increased expression of MHC II molecules compared to the control group without rCts L exposure. Interestingly, Cts L levels were higher in DC than macrophages in most tissues of piglets infected with M. hyopneumoniae (Zhang et al, 2019).…”