Modulation of Mycobacterium tuberculosis-specific humoral immune responses is associated with Strongyloides stercoralis co-infection

Background / Objectives Helminth infections are known to influence T cell responses in latent tuberculosis (LTBI). Whether helminth infections also modulate B cell responses in helminth-tuberculosis co-infection is not known. Methods We assessed Mycobacterium tuberculosis (Mtb)–antigen specific IgM and IgG levels, circulating levels of the B cell growth factors, BAFF and APRIL and the absolute numbers of the various B cell subsets in individuals with LTBI, LTBI with coincident Strongyloides stercoralis (Ss) infection (LTBI/Ss) and in those with Ss infection alone (Ss). We also measured the above-mentioned parameters in the LTBI-Ss group after anthelmintic therapy. Results Our data reveal that LTBI-Ss exhibit significantly diminished levels of Mtb-specific IgM and IgG, BAFF and APRIL levels in comparison to those with LTBI. Similarly, those with LTBI-Ss had significantly diminished numbers of all B cell subsets (naïve, immature, classical memory, activated memory, atypical memory and plasma cells) compared to those with LTBI. There was a positive correlation between Mtb—antigen specific IgM and IgG levels and BAFF and APRIL levels that were in turn related to the numbers of activated memory B cells, atypical memory B cells and plasma cells. Finally, anthelmintic treatment resulted in significantly increased levels of Mtb—antigen specific IgM and IgG levels and the numbers of each of the B cell subsets. Conclusions Our data, therefore, reveal that Ss infection is associated with significant modulation of Mtb-specific antibody responses, the levels of B cell growth factors and the numbers of B cells (and their component subsets).
Author summary Helminth infections and tuberculosis are two of the major health care problems worldwide and share a great deal of geographical overlap. Moreover, helminth infections are known to induce immune responses that are antagonistic to the protective immune responses elicited by Mycobacterium tuberculosis. Having previously demonstrated that helminth infections can profoundly alter protective T cell responses needed to control tuberculosis infection, we examined how Strongyloides stercoralis (Ss) infection influences B cell responses in latent tuberculosis infection (LTBI) in the context of co-infection and showed the Ss infection is associated with dramatic alterations in mycobacterial-specific IgG and IgM responses and levels of B cells and their growth factors BAFF and APRIL. These alterations in B cell responses could have implications for vaccine-induced immune responses to tuberculosis in helminth—endemic countries.