Helminth infection is associated with dampened cytokine responses to viral and bacterial stimulations in Tsimane forager-horticulturalists

Abstract

Background Soil-transmitted helminths (STHs) and humans share long co-evolutionary histories over which STHs have evolved strategies to permit their persistence by downregulating host immunity. Understanding the interactions between STHs and other pathogens can inform our understanding of human evolution and contemporary disease patterns. Methodology We worked with Tsimane forager-horticulturalists in the Bolivian Amazon, where STHs are prevalent. We tested whether STHs and eosinophil levels—likely indicative of infection in this population—are associated with dampened immune responses to in vitro stimulation with H1N1 and lipopolysaccharide (LPS) antigens. Whole blood samples (n = 179) were treated with H1N1 vaccine and LPS and assayed for 13 cytokines (INF-, IL-1, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, GM-CSF, and TNF-ɑ). We evaluated how STHs and eosinophil levels affected cytokine responses and T helper (Th) 1 and Th2- cytokine suite responses to stimulation. Results Infection with Ascaris lumbricoides was significantly (p ≤ 0.05) associated with lower response of some cytokines to H1N1 and LPS in women. Eosinophils were significantly negatively associated with some cytokine responses to H1N1 and LPS, with the strongest effects in women, and associated with a reduced Th1- and Th2-cytokine response to H1N1 and LPS in women and men. Conclusions and implications Consistent with the ‘old friends’ and hygiene hypotheses, we find that STHs were associated with dampened cytokine responses to certain viral and bacterial antigens, suggesting that STH infections may play an essential role in immune response regulation, and suggest that the lack STH immune priming in industrialized populations may increase the risk of over-reactive immunity. LAY SUMMARY Indicators of helminth infection were associated with dampened cytokine immune responses to in vitro stimulation with viral and bacterial antigens in Tsimane hunter-horticulturalists in the Bolivian Amazon, consistent with the ‘old friends’ and hygiene hypotheses.

Urinary neopterin reflects immunological variation associated with age, helminth parasitism, and the microbiome in a wild primate

“…Specifically, we assess whether neopterin captures age-related variation in baseline inflammation, expecting to observe the highest neopterin in the youngest and oldest individuals. We also evaluate whether urinary neopterin captures (1) inflammation associated with the intramuscular larval tapeworm Taenia serialis , which infects wild geladas and causes protuberant cysts that substantially increase mortality 39 , 40 , (2) regulatory and anti-inflammatory effects of gastrointestinal parasite infection 41 , and (3) characteristics of the gastrointestinal microbiota that reflect dysregulation (i.e., low alpha diversity, abundance of pathogenic bacteria).…”

A New Role for Old Friends: Effects of Helminth Infections on Vaccine Efficacy

“…Nutman et al report that vaccination efficacy with the live oral cholera vaccine CVD 103-HgR is associated with a Th1 cytokine response (IL-2 and IFN-γ) to cholera toxin B subunit (CT-B), while infection with A. lumbricoides diminishes the magnitude of this response and ALB treatment before vaccination can partially reverse the deficit in IL-2 [ 59 ]. Consistent with the ‘old friends’ hypotheses, A. lumbricoides infection is associated with dampened Th1 cytokine immune responses to in vitro stimulation with H1N1 and lipopolysaccharide (LPS) antigens in Tsimane forager-horticulturalists in the Bolivian Amazon [ 40 ]. In addition, S. mansoni infection results in reduced protective efficacy against hepatitis B and tetanus vaccines in adults in western Kenya, and increased IL-5 concentration is observed in vitro cultures of peripheral blood mononuclear cells (PBMC) [ 21 ].…”

Ecoimmunology in the field: Measuring multiple dimensions of immune function with minimally invasive, field‐adapted techniques

“…Antigen stimulation assays involve mixing blood with an antigen or mitogen and incubating in medium, followed by measurement of the response to the treatment. Common antigens include lipopolysaccharide (LPS), a cell wall component of gram-negative bacteria that initiates B-cell division and activation of antigen presenting cells, and phytohemagglutinin (PHA) a mitogen that activates T cells; other studies have also used antigens ranging from fragments of helminths (van Riet et al, 2009) to H1N1 flu vaccine (Schneider-Crease et al, 2021). Typical protocols call for incubation in a CO 2 enriched incubator at 37 C. However, developed a field-friendly method for whole blood stimulation that does not require the CO 2 tank.…”

“…Lang et al, 2011; den Braber et al, 2012; Cho et alvan Den Biggelaar, et al, 2009;van Riet et al, 2009;Trumble et al, 2016;Schneider-Crease et al…”