Helminth species specific expansion and increased TNF-alpha production of non-classical monocytes during active tuberculosis

PLoS Negl Trop Dis. 2021 Mar 2;15(3):e0009194. doi: 10.1371/journal.pntd.0009194. eCollection 2021 Mar.


Both Mycobacterium tuberculosis infection and helminths may affect innate immune mechanisms such as differential effects on monocytes towards the non-classical and intermediate subsets that favor bacterial persistence. Our aim, was to investigate helminth species specific effects on the frequency and functional activity of monocyte subsets in patients with active tuberculosis and healthy subjects. HIV-negative patients with active pulmonary tuberculosis (PTB) and community controls (CCs) in Gondar, Ethiopia were screened for helminth infection by stool microscopy. Flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and ex vivo stimulation with purified protein derivative (PPD) and helminth antigens were used to characterize the distribution of monocyte subsets and their function. A total of 74 PTB patients and 57 CCs with and without helminth infection were included. Non-classical monocytes were increased in PTB patients with Ascaris and hookworm infection but not in Schistosoma-infected patients. Ascaris had the strongest effect in increasing the frequency of non-classical monocytes in both PTB patients and CCs, whereas PTB without helminth infection did not affect the frequency of monocyte subsets. There was a helminth specific increase in the frequency of TNF-α producing non-classical monocytes in hookworm infected PTB patients, both with and without PPD-stimulation. Low-to-intermediate TB disease severity associated with increased frequency of non-classical monocytes only for helminth-positive PTB patients, and the frequency of TNF-α producing monocytes were significantly higher in intermediate and non-classical monocytes of helminth positive PTB patients with an intermediate disease score. Helminth infection affected the frequency of monocyte subsets and function both in TB patients and controls which was helminth species dependent in TB patients. The clinical role of this potential immunomodulatory effect needs further study and may affect the response and protection to tuberculosis in areas where helminth infections are endemic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antigens, Helminth
  • Case-Control Studies
  • Coinfection
  • Ethiopia
  • Female
  • Helminthiasis / immunology
  • Helminthiasis / pathology*
  • Helminths / physiology
  • Humans
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Middle Aged
  • Parasite Egg Count
  • Tuberculosis, Pulmonary / immunology*
  • Tuberculosis, Pulmonary / pathology
  • Tumor Necrosis Factor-alpha / metabolism*


  • Antigens, Helminth
  • Tumor Necrosis Factor-alpha

Grants and funding

This work was funded by the Swedish Heart-Lung Foundation (20160431 and 20190484 to RB) and the Swedish Research Council (2017-05617 to RB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.