Common Parasite Weakens Immune Response to Tuberculosis
Researchers discovered that a widespread intestinal parasite dampens the body's ability to fight tuberculosis by altering how immune cells communicate. The finding has direct implications for TB control programs in developing regions where both infections are endemic, potentially explaining why some patients fail standard treatments.
Originaltitel: Ascaris lumbricoides antigen exposure modulates T cell activation via regulation of IL-15Rα expression, STAT5 phosphorylation, and promotes differentiation of BCL6low B cells
Background Mycobacterium tuberculosis (Mtb) causes active tuberculosis (TB) in approximately 10 million people annually, resulting in 1.6 million deaths. TB and helminthiasis have a significant geographical overlap, and helminth infections can trigger immunological responses that dampen Th1 immunity, which is essential for Mtb containment. While B cells are known to modulate T cell responses, their role during helminth/TB co-infection remains unclear. Objective This study aimed to analyze the effect of helminth exposure on T cell activation in a T and B cell co-culture system. Methods T and B cells were isolated from healthy donor blood, stimulated with aCD3/aCD28, and exposed to Ascaris lumbricoides protein antigens (ASC) or Schistosoma mansoni soluble egg antigen (SM). Results B cells reduced T cell proliferation, and SM exposure partly attenuated this inhibitory effect on CD4 T cells. ASC exposure did not affect T cell proliferation but increased soluble IL-15Rα and surface IL-15Rα and IL-2/15Rβ on CD4 T cells. Restimulation with recombinant human IL-15 revealed reduced and unsustained STAT5 activation in CD4 and CD8 T cells in ASC-exposed co-cultures. Additional analysis showed altered phosphorylation of STAT1, STAT3, and STAT6, indicating broader impairment of IL-15 responsiveness and a dampened Th1 activation profile. BCL6/BLIMP-1 transcription factor expression of B cells in ASC-exposed co-cultures suggested a shift toward a more differentiated phenotype, such as plasma cell, memory B cells, or marginal zone MZ B cells, which are all typically BCL6 low . The in vivo analysis of peripheral blood mononuclear cells from individuals in a helminth/TB endemic region showed increased frequencies of CD38 hi CD24 hi B regulatory cells in helminth infected, and MZ B cells (IgM high unswitched B cells) in both helminth-infected and helminth/TB co-infected individuals. Conclusion ASC antigen exposure modulates T cell activation through dynamic regulation of the IL-15-pathway and STAT signaling. These findings suggest that ASC exposure may help prevent prolonged IL-15-driven responses, potentially limiting excessive inflammation during TB. B cells in ASC-exposed co-cultures exhibit transcriptional changes consistent with a shift away from the germinal center phenotype toward more differentiated states.