Filarial Infection Suppresses Malaria-Specific Multifunctional Th1 and Th17 Responses in Malaria and Filarial Coinfections

Abstract

The mechanisms underlying the modulation of both the malaria-specific immune response and the course of clinical malaria in the context of concomitant helminth infection are poorly understood. We used multiparameter flow cytometry to characterize the quality and the magnitude of malaria-specific T cell responses in filaria-infected and -uninfected individuals with concomitant asymptomatic Plasmodium falciparum malaria in Mali. In comparison with filarial-uninfected subjects, filarial infection was associated with higher ex vivo frequencies of CD4+ cells producing IL-4, IL-10, and IL-17A (p = 0.01, p = 0.001, and p = 0.03, respectively). In response to malaria Ag stimulation, however, filarial infection was associated with lower frequencies of CD4+ T cells producing IFN-γ, TNF-α, and IL-17A (p < 0.001, p = 0.04, and p = 0.04, respectively) and with higher frequencies of CD4+IL10+T cells (p = 0.0005). Importantly, filarial infection was associated with markedly lower frequencies of malaria Ag-specific Th1 (p < 0.0001), Th17 (p = 0.012), and “TNF-α” (p = 0.0008) cells, and a complete absence of malaria-specific multifunctional Th1 cells. Filarial infection was also associated with a marked increase in the frequency of malaria-specific adaptive regulatory T/Tr1 cells (p = 0.024), and the addition of neutralizing anti–IL-10 Ab augmented the amount of Th1-associated cytokine produced per cell. Thus, among malaria-infected individuals, concomitant filarial infection diminishes dramatically the frequencies of malaria-specific Th1 and Th17 T cells, and alters the quality and magnitude of malaria-specific T cell responses.

Differential induction of Th2- And Th1-associated responses by filarial antigens and endosymbioticWolbachiain a murine model of river blindness

“…Expression of T-bet also negatively regulates generation of Th17 cells as shown by overwhelming IL-17 production in T-bet −/− mice following immunization with soluble schistosome egg antigen [19]. IL-17 expression was also found increased in filarial-infected patients compared with uninfected patients [20]; however, the role of IL17 was not subject of this study.…”

Helminth Infections and Host Immune Regulation

“…Immunopathologies such as asthma, autoimmune diseases, and inflammatory bowel diseases are all reduced in prevalence in areas where helminth disease is endemic, and direct effects of helminth infections on the suppression of disease have been shown in clinical trials for inflammatory bowel diseases. malaria are both endemic, PBMCs from filaria-infected subjects produced less IL-12p70, IL-17A, and IFN-␥ but more IL-10 in response to malaria antigen (196,197), consistent with diminished IL-12 responses from filariasis patients stimulated with malarial antigen (198).…”

Community deworming alleviates geohelminth-induced immune hyporesponsiveness

“…These had not been specifically investigated in anthelmintic treatment RCTs. However, in cross-sectional studies examining the effect of helminths on malaria-specific cytokine responses, results are inconsistent (17)(18)(19). The increase in response to malaria antigens could be due to a concurrent increase in malarial parasitemia in the albendazole-treated group 6 mo after initiation of treatment (20), coincident with peak transmission season.…”