Abstract
The filarial nematode Mansonella perstans is endemic throughout Africa, northern South America and the Caribbean. Interestingly, M. perstans-infected individuals present no distinct clinical picture associated with certain pathology. Due to its relatively silent nature, research on this tropical disease has been neglected, especially M. perstans-driven immune responses. A hindrance in obtaining data on M. perstans-specific responses has been the inability to obtain adult worms since their habitats in serous cavities are difficult to access. Thus, in this study, for the first time, we used Mansonella perstans worm antigen extract as stimulant to obtain filarial-specific recall and immunoglobulin responses from M. perstans microfilaremic individuals (Mp MF+) from Cameroon. Moreover, systemic immune profiles in sera and immune cell composition in peripheral blood from Mp MF+ and amicrofilaremic individuals (Mp MF-) were obtained. Our data reveal that Mp MF+ individuals showed significantly reduced cytokine (IL-4, IL-6 and IL-12p70) and chemokine levels (IL-8 and RANTES), but significantly higher MIP-1β as well as increased M. perstans-specific IgG4 levels compared to Mp MF- individuals. In contrast, upon re-stimulation with worm antigen extract, IFN-γ, IL-13, IL-10 and IL-17A secretion was enhanced in cell cultures from Mp MF+ individuals when compared to those from cultures of healthy European individuals. Moreover, analysis of immune cell composition in peripheral blood from Mp MF+ individuals revealed increased type 2 helper T (Th2), natural killer (NK), regulatory B and T cell (Breg and Treg) subsets but decreased type 1 regulatory T (Tr1) cells. In summary, this study deciphers for the first time, M. perstans-specific immune responses using worm antigen extract and shows that patent M. perstans infections have distinct Th2, Breg and Treg subsets accompanied with reduced systemic innate and adaptive immune responses and dominant filarial-specific IgG4 levels.
Highlights
Worldwide approximately 240 million individuals are known to be infected with tropical threadlike nematodes from the family Onchocercidae and infections can persist for numerous years in man due to the helminth’s immunomodulatory capacity on the host’s immune system [1,2,3,4,5,6,7]
M. perstans currently poses a potential risk to 581 million people throughout Africa and for many years infections were considered to be nonpathogenic because individuals presented undefined and non-distinct clinical symptoms
We applied for the first time M. perstans worm antigen extract in order to test its re-stimulation capacity on cells isolated from M. perstans-microfilaremic individuals
Summary
Worldwide approximately 240 million individuals are known to be infected with tropical threadlike nematodes from the family Onchocercidae and infections can persist for numerous years in man due to the helminth’s immunomodulatory capacity on the host’s immune system [1,2,3,4,5,6,7]. The well-adapted filarial helminth Mansonella perstans is endemic in tropical parts of Latin America and large proportions of Africa, with an estimated infection rate of 114 million people in over 33 countries [8]. Research with M. perstans has been hindered by the lack of specific antigen since adult worms reside in body cavities: the pericardium, the mesentery, and the perirenal and retroperitoneal connective tissues and are only rarely recovered [8,9,10]. In many endemic areas the Culicoides species that transmits M. perstans remains unclear. The exact chronology of M. perstans adult worm development remains ambiguous, fecund adult females release numerous microfilariae (MF), which circulate in the peripheral blood and can be taken up by another Culicoides biting midge to complete the cycle [8,9,10]
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