Helminth mediated modulation of the systemic and mycobacterial antigen - stimulated cytokine profiles in extra-pulmonary tuberculosis

PLoS Negl Trop Dis. 2019 Mar 21;13(3):e0007265. doi: 10.1371/journal.pntd.0007265. eCollection 2019 Mar.

Abstract

Background: Helminth infections are known to regulate cytokine responses in both pulmonary and latent tuberculosis infection. Whether helminth infections also modulate cytokine responses in extra-pulmonary tuberculosis, specifically tuberculous lymphadenitis (TBL), has not been examined thus far.

Methodology: Hence, to determine the cytokine profile in helminth-TBL coinfection, we measured the systemic and mycobacterial (TB)-antigen stimulated levels of Type 1, Type 2, Type 17, regulatory and pro-inflammatory cytokines in TBL individuals coinfected with or without Strongyloides stercoralis (Ss) infection.

Significant findings: TBL-Ss+ individuals have significantly higher bacterial burdens in the affected lymph nodes in comparison to TBL-Ss- individuals. TBL-Ss+ individuals exhibit significantly enhanced plasma levels of Type 2 (IL-5 and IL-13), Type 17 (IL-17 and IL-22) and regulatory (IL-10) cytokines in comparison to TBL-Ss- individuals. In contrast, TBL-Ss+ individuals exhibit significantly diminished plasma levels of pro-inflammatory cytokines (IL-1α and GM-CSF) in comparison to TBL-Ss- individuals. TBL-Ss+ individuals also exhibit significantly diminished unstimulated or mycobacterial-antigen stimulated levels of Type 1, Type 17 or IL-1 family cytokines in comparison to TBL-Ss- individuals but no differences in mitogen stimulated cytokine levels.

Conclusion: Therefore, our data reveal a profound influence of Ss infection on the bacteriological profile of TBL and suggesting that the underlying modulation of cytokine responses might be a mechanism by which this helminth infection could impart a detrimental effect on the pathogenesis of TBL disease.

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antigens, Bacterial / immunology*
  • Coinfection
  • Cytokines / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • Strongyloides stercoralis / physiology*
  • Strongyloidiasis / complications
  • Strongyloidiasis / immunology*
  • Strongyloidiasis / parasitology
  • Tuberculosis, Lymph Node / complications
  • Tuberculosis, Lymph Node / immunology*
  • Tuberculosis, Lymph Node / microbiology
  • Young Adult

Substances

  • Antigens, Bacterial
  • Cytokines

Grants and funding

The author (GRK) thank the Indian Council of Medical Research (ICMR), New Delhi, India for the ICMR-PDF award. This work was also supported by the Division of Intramural Research, NIAID, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.