IFN-γ fails to overcome inhibition of selected macrophage activation events in response to pathogenic mycobacteria

PloS One
Shyamala ThirunavukkarasuKumudika de Silva

Abstract

According to most models of mycobacterial infection, inhibition of the pro-inflammatory macrophage immune responses contributes to the persistence of bacteria. Mycobacterium avium subsp. paratuberculosis (MAP) is a highly successful pathogen in cattle and sheep and is also implicated as the causative agent of Crohn's disease in humans. Pathogenic mycobacteria such as MAP have developed multiple strategies to evade host defence mechanisms including interfering with the macrophages' capacity to respond to IFN-γ, a feature which might be lacking in non-pathogenic mycobacteria such as M. smegmatis. We hypothesized that pre-sensitisation of macrophages with the pro-inflammatory cytokine IFN-γ would help in overcoming the inhibitory effect of MAP or its antigens on macrophage inflammatory responses. Herein we have compared a series of macrophage activation parameters in response to MAP and M. smegmatis as well as mycobacterial antigens. While IFN-γ did overcome the inhibition in immune suppressive mechanisms in response to MAP antigen as well as M. smegmatis, we could not find a clear role for IFN-γ in overcoming the inhibition of macrophage inflammatory responses to the pathogenic mycobacterium, MAP. We demonstrate that suppression ...Continue Reading

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Citations

Oct 10, 2019·Journal of Cellular and Molecular Medicine·Xinyuan WangNing Huang
Feb 27, 2020·Current Opinion in Pulmonary Medicine·Grant Waterer
Apr 25, 2018·Microbiology and Immunology·Shivendra K Chaurasiya
Oct 3, 2020·Biomarker Research·Dragica JorgovanovicYi Zhang
May 7, 2019·Frontiers in Cellular and Infection Microbiology·Shyamala Thirunavukkarasu, Shabaana A Khader

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Methods Mentioned

BETA
FCS
nuclear translocation
flow cytometry
ubiquitination

Software Mentioned

Image ProPlus
Genstat
Quantigene
CellQuest Pro
FlowCytomix Pro
ImageProPlus

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