학술논문
Individuals co-exposed to sand fly saliva and filarial parasites exhibit altered monocyte function.
Document Type
article
Author
Moussa Sangare; Yaya Ibrahim Coulibaly; Naureen Huda; Silvia Vidal; Sameha Tariq; Michel Emmanuel Coulibaly; Siaka Yamoussa Coulibaly; Lamine Soumaoro; Ilo Dicko; Bourama Traore; Ibrahim Moussa Sissoko; Sekou Fantamady Traore; Ousmane Faye; Thomas B Nutman; Jesus G Valenzuela; Fabiano Oliveira; Seydou Doumbia; Shaden Kamhawi; Roshanak Tolouei Semnani
Source
PLoS Neglected Tropical Diseases, Vol 15, Iss 6, p e0009448 (2021)
Subject
Language
English
ISSN
1935-2727
1935-2735
1935-2735
Abstract
BackgroundIn Mali, cutaneous leishmaniasis (CL) and filariasis are co-endemic. Previous studies in animal models of infection have shown that sand fly saliva enhance infectivity of Leishmania parasites in naïve hosts while saliva-specific adaptive immune responses may protect against cutaneous and visceral leishmaniasis. In contrast, the human immune response to Phlebotomus duboscqi (Pd) saliva, the principal sand fly vector in Mali, was found to be dichotomously polarized with some individuals having a Th1-dominated response and others having a Th2-biased response. We hypothesized that co-infection with filarial parasites may be an underlying factor that modulates the immune response to Pd saliva in endemic regions.Methodology/principal findingsTo understand which cell types may be responsible for polarizing human responses to sand fly saliva, we investigated the effect of salivary glands (SG) of Pd on human monocytes. To this end, elutriated monocytes were cultured in vitro, alone, or with SG, microfilariae antigen (MF ag) of Brugia malayi, or LPS, a positive control. The mRNA expression of genes involved in inflammatory or regulatory responses was then measured as were cytokines and chemokines associated with these responses. Monocytes of individuals who were not exposed to sand fly bites (mainly North American controls) significantly upregulated the production of IL-6 and CCL4; cytokines that enhance leishmania parasite establishment, in response to SG from Pd or other vector species. This selective inflammatory response was lost in individuals that were exposed to sand fly bites which was not changed by co-infection with filarial parasites. Furthermore, infection with filarial parasites resulted in upregulation of CCL22, a type-2 associated chemokine, both at the mRNA levels and by its observed effect on the frequency of recruited monocytes.Conclusions/significanceTogether, our data suggest that SG or recombinant salivary proteins from Pd alter human monocyte function by upregulating selective inflammatory cytokines.