Regulation of immune responses toStrongyloides venezuelensischallenge after primary infection with different larvae doses

Abstract

Nematode infections are generally followed by high rates of reinfection, leading to elevated prevalence in endemic areas. Therefore, the effective control of nematode infections depends on understanding the induction and regulation of protective mechanisms. However, most experimental models for protective immune response against nematodes use high parasite exposure, not always reflecting what occurs naturally in human populations. In this study, we tested whether infecting mice with different Strongyloides venezuelensis larvae loads would affect protective responses against reinfection. Interestingly, we found that a previous infection with 10-500 larvae conferred high rate of protection against reinfection with S. venezuelensis in mice, by destroying large numbers of migrating larvae. However, low-dose priming did not abolish adult worm maturation, as detected in high-dose primed group. Results also indicated that a previous low-dose infection delayed the development of cellular infiltrate, while a high inoculum rapidly induced these inflammatory features. Cytokine production by splenocyte cultures of challenge infected mice demonstrated that low-dose priming had increased production of IL-4 and IFN-gamma, while high-dose induced IL-4 production but not IFN-gamma. Our data support the hypothesis that low-dose nematode infection does not induce a polarized type-2 immune response, allowing adult worm survival.

Protection against Nippostrongylus brasiliensis infection in mice is independent of GM‐CSF

“…When mice were given a second infection with N. brasiliensis , all groups showed decreased worm burden in both the lung and intestinal phases, and decreased egg production, compared with primary infection. These results indicate the development of protective immunity, which has been reported as a feature of N. brasiliensis and certain other parasite infections 17 , 23 , 24 . In the secondary infection, there was no increase in parasite burden in the ΔGM‐CSF mice compared with the WT mice.…”

Multiple Exposures to Ascaris suum Induce Tissue Injury and Mixed Th2/Th17 Immune Response in Mice

“…While an increased activity of eosinophils in mice reinfected with S . stercoralis was not directly associated with destruction of parasitic larvae [ 30 ], in our study we observed that a remarkable rise in count and activity of eosinophils was followed by a substantial reduction in the parasitic burden, suggesting the importance of eosinophils in the clearance of Ascaris infection [ 32 ]. On the other hand, the presence of eosinophils would be implicated in tissue repair and remodeling due to the extensive lung injury and hemorrhage associated with migration of larvae into airways, which lead to alveolar edema and robust inflammation and to further changes in pulmonary functions detected by spirometry.…”

“…Thus, IL-10 might control inflammation as IL-4 may mediate tissue healing by promoting the response from macrophages and eosinophils [ 42 , 43 , 46 , 49 ]. Moreover, while previous studies demonstrated that IL-4 and IL-10 have inhibitory effects on IL-17A [ 30 , 40 ], the presence of systemic production of these cytokines in animals that were repeatedly exposured to A . suum was not yet clear.…”

“…suum [ 25 ], Strongyloides ratti [ 26 ], Neodiplostomum seoulensis [ 27 , 28 ], Clonorchis sinensis [ 29 ] and S . stercoralis [ 30 ], amongst other helminths. The current study also provides strong evidence that multiple exposures to A .…”

Increased susceptibility to Strongyloides venezuelensis infection is related to the parasite load and absence of major histocompatibility complex (MHC) class II molecules

“…In human and murine models the infection is characterized by systemic eosinofilia (Korenaga et al, 1991;Nawa et al, 1994;Onah and Nawa, 2000), production of cytokines such as IL-3, IL-4, IL-5 and IL-13 with subsequent secretion of specific IgM, IgG, IgG1, IgA and IgE, essential to the elimination of the parasite (Abe and Nawa, 1988;Onah and Nawa, 2000;Schilter et al, 2010;Goncalves et al, 2012a). S. venezuelensis naturally infects rats and has been used in experimental models (Machado et al, 2005;Negrão-Correa et al, 2006) aimed to study the immunoprotection and immunoregulation aspects of the disease since it evokes similar innate and acquired immune response in mice as does S. stercoralis in humans (Rodrigues et al, 2009).…”