Abstract
Mycobacterium tuberculosis (Mtb) and helminth infections elicit antagonistic immune effector functions and are co-endemic in several regions of the world. We therefore hypothesized that helminth infection may influence Mtb-specific T-cell immune responses. We evaluated the cytokine profile of Mtb-specific T cells in 72 individuals with pulmonary TB disease recruited from two Sub-Saharan regions with high and moderate helminth burden i.e. 55 from Tanzania (TZ) and 17 from South Africa (SA), respectively. We showed that Mtb-specific CD4 T-cell functional profile of TB patients from Tanzania are primarily composed of polyfunctional Th1 and Th2 cells, associated with increased expression of Gata-3 and reduced expression of T-bet in memory CD4 T cells. In contrast, the cytokine profile of Mtb-specific CD4 T cells of TB patients from SA was dominated by single IFN-γ and dual IFN-γ/TNF-α and associated with TB-induced systemic inflammation and elevated serum levels of type I IFNs. Of note, the proportion of patients with Mtb-specific CD8 T cells was significantly reduced in Mtb/helminth co-infected patients from TZ. It is likely that the underlying helminth infection and possibly genetic and other unknown environmental factors may have caused the induction of mixed Th1/Th2 Mtb-specific CD4 T cell responses in patients from TZ. Taken together, these results indicate that the generation of Mtb-specific CD4 and CD8 T cell responses may be substantially influenced by environmental factors in vivo. These observations may have major impact in the identification of immune biomarkers of disease status and correlates of protection.
Highlights
Helminth infections are endemic in many African countries with different prevalence depending on the geographic region helminth species and age of population [1]
We hypothesized that helminth infection would impact and potentially shape Mycobacterium tuberculosis (Mtb)-specific T-cell responses and systemic inflammation in patients suffering from active pulmonary tuberculosis (TB) enrolled from two helminth endemic regions i.e. Tanzania (TZ) and South Africa (SA)
We demonstrate for the first time that tuberculosis disease (TB) patients from SA and TZ harbor distinct immune responses to Mtb antigens
Summary
Helminth infections are endemic in many African countries with different prevalence depending on the geographic region helminth species and age of population [1]. Helminth infections are co-endemic in many geographic areas endemic for Mycobacterium tuberculosis (Mtb), HIV-1 and Plasmodium falciparum. Co-infections of helminths with Mtb, HIV-1 and/or Plasmodium falciparum occur in a large proportion of the subjects [3]. Mycobacterium tuberculosis (Mtb) is a facultative intracellular organism, obligate aerobe, infecting primarily lungs via the aerogenic route [4]. It has been recently estimated that 1.7 billion people are infected with Mtb among which 5–15% will develop tuberculosis disease (TB) [5]. While BCG immunization protects from life-threatening disseminated forms of TB disease in children, its efficacy in adults is inconsistent [6]. Several studies have underscored the essential role of IL-12/IFN-γ axis in the protection against Mtb infection [7,8,9,10]. An efficient CD4 T-cell response probably associated with type 1 cytokine secretion is associated with the control of Mtb infection, since a severe reduction in the CD4 T cell number during HIV infection or the suppression of their function following anti-TNF-α therapy are associated with increased risk of TB reactivation [11, 12]
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