Comparison Between Phenotypic Profile and Functional Aspects of IL-9-Producing Lymphocytes, Th17 and Tfh of Individuals From Endemic and Non-Endemic Areas for Hookworm Infection.

Abstract

Hookworm infections remain a major public health concern in endemic areas, modulating both the adaptive and innate immune systems. While the type 2 response is well-characterised, the roles of T follicular helper (Tfh), Th17, and IL-9-producing lymphocytes remain poorly defined. Here, we characterised these T cell subsets in individuals naturally infected with hookworms. From 1500 faecal samples screened, 60 were positive for hookworms, and peripheral blood was collected from 10 uninfected controls from endemic (NEG END) and non-endemic (NEG NE) areas, as well as from 7 infected individuals before (HKW BT) and after (HKW PT) treatment. Infected individuals displayed haematological alterations, including anaemia (n = 2), eosinophilia (n = 1), monocytosis (n = 4), and lymphocytosis (n = 3), along with an expansion of PBMCs, particularly Tfh cells, during infection. Expression of IL-9 and IL-10 by Tfh cells was markedly elevated after treatment. In contrast, individuals from non-endemic areas displayed a distinct baseline profile with higher Tfh activation (CD69) expression, suggesting immune adaptation in endemic settings. While IL-10-producing Tfh expanded during infection, IL-9-producing cells and Th17 cells expanded mainly after treatment. These findings suggest that individuals living in endemic areas, regardless of infection status, exhibit signs of persistent antigenic stimulation that promote a more tolerogenic and regulated immune profile. Moreover, hookworm infection and subsequent treatment reshape the immune landscape, highlighting the contribution of Tfh- and Th17-associated pathways, as well as IL-9 and IL-10 production, in modulating host-parasite interactions.