Strongyloides stercoralis coinfection impairs immune control of Mycobacterium tuberculosis in TB infected individuals

TL;DR

This study shows that a parasitic infection worsens immune responses to tuberculosis, suggesting that treating co-infections could improve TB control.

Contribution

The study reveals that Strongyloides stercoralis co-infection skews immune responses in TB, impairing protective Th1/Th17 pathways.

Findings

TBI+Hel+ individuals showed reduced mycobacterial growth inhibition compared to TBI+Hel− individuals.

Th1/Th17 and proinflammatory cytokines were suppressed in TBI+Hel+ individuals.

Th2/regulatory cytokines were elevated in TBI+Hel+ individuals.

Abstract

Helminth co-infection are common in tuberculosis (TB) endemic regions and alter host immunity. However, their impact on immune responses in TB infection (TBI) remains incompletely defined.

We analyzed QuantiFERON (QFT) supernatants and peripheral blood mononuclear cells (PBMCs) from TBI+Hel+ (S. stercoralis(Ss) infection) (n=15) and TBI+Hel− (n=23) individuals. Cytokine levels were assessed at baseline and following TB antigenic stimulation (TBAg1 and TBAg2), as well as mitogenic stimulation. PBMCs were stimulated with Mycobacterium tuberculosis (M. tuberculosis) H37Rv, and antimycobacterial immunity was assessed using an in vitro mycobacterial growth inhibition assay (MGIA) and multiplex cytokine assays.

We measured Type 1 (IFN-γ, TNF-α, IL-2), Type 17 (IL-17, IL-22), and proinflammatory cytokines (IL-1α, IL-1β) in QuantiFERON (QFT) supernatants from TBI individuals with (TBI+Hel+) and without (TBI+Hel−) infection. TBI+Hel+ individuals exhibited significantly reduced mycobacterial growth inhibition compared with TBI+Hel− individuals, reflected by higher normalized mycobacterial growth (Δ log10 CFU). Cytokine analysis showed suppression of Th1/Th17 (IFN-γ, IL-2, TNF-α, IL-17, GM-CSF) and proinflammatory cytokines (IL-1α, IL-1β, IL-6, IL-12p70, IL-18) in TBI+Hel+ individuals, alongside increased Th2/regulatory cytokines (IL-4, IL-5, IL-10, IL-13).

Ss co-infection impairs host antimycobacterial control by skewing TBI immune responses toward Th2/regulatory pathways at the expense of protective Th1/Th17 mechanisms. Our data demonstrate that the importance of considering Ss co-infection into account when developing TB control and vaccination strategies in endemic areas.

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