HIV-1 and the Mycobacterium tuberculosis granuloma: A systematic review and meta-analysis

Abstract

Infection with HIV-1 greatly increases the risk of active tuberculosis (TB). Although hypotheses suggest HIV-1 disrupts Mycobacterium tuberculosis (Mtb) granuloma function, few studies have examined this directly. The objective of this study was to determine what evidence exists about the effect HIV-1 co-infection has upon Mtb granulomas. A systematic search of PubMed, Web of Science, and Medline up to 20 March 2015 was conducted, to identify studies comparing Mtb-infected tissue from HIV-1 infected and uninfected persons, or HIV-1 infected persons with stratified peripheral CD4 T cell (pCD4) counts. We summarized findings that focused on how HIV-1 changes granuloma formation, bacterial presence, cellular composition, and cytokine production. Nineteen studies with a combined sample size of 899 persons were included. Although studies frequently were limited by variable or inadequately described definitions of outcomes and analytical methods, HIV-1 was found to be associated with increased bacillary load within Mtb-infected tissue. Reductions in pCD4 counts within co-infected persons associated with both poorer granuloma formation and higher bacterial load. The high degree of heterogeneity among studies combined with experimental limitations made it difficult to conclusively support previously published and prevalent hypotheses about HIV-1/Mtb co-infection granulomas. To elucidate the validity of these hypotheses we have described areas that can be improved in future studies in order to clarify the influence HIV-1 co-infection has upon the Mtb granuloma.

Relationship Between HIV Coinfection, Interleukin 10 Production, andMycobacterium tuberculosisin Human Lymph Node Granulomas

“…HIV infection has also been shown in vitro to increase the growth of M. tuberculosis in coinfected macrophages [10, 11], but such responses are highly variable [12]. Although these studies demonstrate that HIV causes specific reductions in the immunological responses to M. tuberculosis , very few studies have clearly demonstrated how HIV changes these responses within granulomas [13], the archetypal microscopic hallmark of tuberculosis-diseased tissue. The immunological function and cellular composition of granulomas significantly varies between granulomas [14] and blood or airways [15], demonstrating the need to examine granulomas directly [16].…”

“…Studies that have examined granulomas in persons with HIV and M. tuberculosis coinfection (hereafter, “coninfected persons”) and those with M. tuberculosis monoinfection are highly variable, and it is difficult to draw firm conclusions about how HIV changes granuloma organization, formation, cellular composition, and M. tuberculosis abundance [13]. The inconsistency of these data partially results from the highly variable and heterogeneous nature of granulomas, a limited number of studies, a low number of persons in the studies, and highly variable and qualitative methods, which make comparisons among multiple studies difficult.…”

Differentiating Crohn’s disease from intestinal tuberculosis at presentation in patients with tissue granulomas

“…This is supported by data showing that reductions in CD4+ counts in co-infected persons were associated with both poorer granuloma formation and higher bacterial load. [14] …”

HIV induced suppression of host immunity: relevance to <i>Mycobacterium tuberculosis</i> infections

“…Specifically, HIV impairs the TNF-α mediated apoptosis of mφ, and thus facilitates the survival of bacilli. Moreover, HIV disintegrates the granuloma organization leading to dissemination of bacilli [49].…”