Kinetics of IFN-Gamma and TNF-Alpha Gene Expression and Their Relationship with Disease Progression after Infection withMycobacterium Tuberculosisin Guinea Pigs

Abstract

PurposeGuinea pig is one of the most suitable animal models for Mycobacterium tuberculosis (M. tb) infection since it shows similarities to pulmonary infection in humans. Although guinea pig shows hematogenous spread of M. tb infection into the whole body, immunological studies have mainly focused on granulomatous tissues in lungs and spleens. In order to investigate the time-course of disease pathogenesis and immunological profiles in each infected organ, we performed the following approaches with guinea pigs experimentally infected with M. tb over a 22-week post-infection period.Materials and MethodsWe examined body weight changes, M. tb growth curve, cytokine gene expression (IFN-γ and TNF-α), and histopathology in liver, spleen, lungs and lymph nodes of infected guinea pigs.ResultsThe body weights of infected guinea pigs did not increase as much as uninfected ones and the number of M. tb bacilli in their organs increased except bronchotracheal lymph node during the experimental period. The gene expression of IFN-γ and TNF-α was induced between 3 and 6 weeks of infection; however, kinetic profiles of cytokine gene expression showed heterogeneity among organs over the study period. Histophathologically granulomatous lesions were developed in all four organs of infected guinea pigs.ConclusionAlthough IFN-γ and TNF-α gene expression profiles showed heterogeneity, the granuloma formation was clearly observed in every organ regardless of whether the number of bacilli increased or decreased. However, this protective immunity was accompanied with severe tissue damage in all four organs, which may lead to the death of guinea pigs.

Multicenter clinical evaluation of three commercial reagent kits based on the interferon-gamma release assay for the rapid diagnosis of tuberculosis in China

“…In a study on cytokine gene expression in the M. tuberculosisinfected guinea pig model, the expression of IFN-g was induced at between 3 and 6 weeks of infection and gradually decreased. 29 Such an effect might have influenced the accuracy of test performance, as the duration of infection in the participants enrolled in this study was unclear.…”

Role of Tissue Factor in Mycobacterium Tuberculosis-induced Inflammation and Disease Pathogenesis

“…It is possible that the close inter-relationship between the coagulation and inflammation may not exist in chronic infections such as TB. Although we cannot rule out the possibility that TF deficiency may have an effect on elaboration of proinflammatory cytokines at the very early stage of the M.tb infection, it is important to note here that expression of inflammatory cytokines in mice and guinea pig following M.tb infection was shown to occur around 2 to 3 weeks post infection, and the expression was persistent for 10 weeks or more [45,46].…”

Automated quantitative assay of fibrosis characteristics in tuberculosis granulomas

“…Several cytokines, such as TNF-α, TGF-β, and MMP-9, are critical for granuloma formation following Mtb infection ( Iliopoulos et al, 2006 ; Taylor et al, 2006 ; Barry et al, 2009 ; Mootoo et al, 2009 ; Beham et al, 2011 ; Fallahi-Sichani et al, 2011 ; Ramakrishnan, 2012 ; Roh et al, 2013 ; Shmarina et al, 2013 ; Al Shammari et al, 2015 ; Datta et al, 2015 ; Ordonez et al, 2016 ; Warsinske et al, 2017 ; Walton et al, 2018 ). Here, we further characterized the profile of those cytokines in clinical tuberculosis human and Mtb -infected model animal tissues and found that MMP-9 was highly expressed.…”