Intestinal mast cell response and mucosal defence against Strongyloides venezuelensis in interleukin‐3‐hyporesponsive mice

Abstract

Recently several inbred strains of mice were found to be hyporesponsive to Interleukin (IL)-3 because of a 5-bp deletion in the intron 7 of the gene that encodes IL-3 receptor alpha subunit (IL-3R alpha). Due to this mutation, mast cells were not generated in vitro from bone marrow cells of these mice under the presence of IL-3. Intestinal mucosal mast cells, of which growth/differentiation is dependent on IL-3, are important effector cells in immune-mediated expulsion of intestinal nematodes, Stronglyoides spp. In the present study, therefore, we examined intestinal mast cell response and mucosal defence against Strongyloides venezuelensis in IL-3-hyporesponsive C58/J and A/J mice. After subcutaneous inoculation with 10,000 infective larvae, C58/J and IL-3-responsive C57BL/6 mice showed identical kinetic patterns of daily faecal egg output and intestinal mast cell response. When these mice were infected with 3000 L3 and, five weeks later, they were challenged by intraduodenal implantation of 800 S. venezuelensis adult worms, the timing of logarithmic decline of faecal egg count as well as intestinal mastocytosis was delayed for two days in C58/J mice. Kinetics of intestinal mastocytosis and faecal egg excretion after a primary and challenge infection in A/J mice, another IL-3-hyporesponsive strain, were identical with those seen in C58/J mice. These results suggest that intestinal mast cell response and mucosal defence against S. venezuelensis of the mutant mice were almost completely compensated in vivo. Possible mechanisms of induction of intestinal mast cell response in IL-3R alpha-defective mice are discussed.

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

“…It was hypothesized that in infection settings with different larvae doses there would be enhanced survival and development of this parasite in mice lacking MHC class II molecules. It is known that both in human hosts and experimental models the infection with Strongyloides sp is characterized by tissue eosinophilia (Korenaga et al, 1991;El-Malky et al, 2003) and intestinal mastocytosis (Abe and Nawa, 1988;Nawa et al, 1994;Kobayashi et al, 1998), with production of Th2-type antibodies (Abe and Nawa, 1988;Machado et al, 2005;Rodrigues et al, 2007;Goncalves et al, 2012b) and cytokines (Maruyama et al, 2000). Here we demonstrated that MHC II À/À mice infected with 3000 L3 exhibited a higher number of eggs recovered from the feces and delayed elimination of adults worms besides increased worm fecundity compared with the other groups, suggesting that S. venezuelensis migration, expulsion or intestinal establishment are affected not only by the host immune competence but also by the amount of parasites to which mice are exposed during infection.…”

NIP45 controls the magnitude of the type 2 T helper cell response

“…S4 C and D). IL-3 production by mesenteric lymphocytes is critical for maintaining intestinal mastocytosis in response to parasitic infection, whereas the addition of exogenous IL-3 during infection accelerates T. spiralis expulsion (38)(39)(40)(41)(42). Thus, we examined the production of IL-3 by mesenteric T helper cells after infection.…”

Leukotrienes Play a Role in the Control of Parasite Burden in Murine Strongyloidiasis

“…In human hosts and in murine models, the immune response to Strongyloides sp is characterized by intraepithelial and tissue increase of eosinophils (8,9), as well as by intestinal mastocytosis (10,11) and production of Th2-type cytokines such as IL-3, IL-4, and IL-5 (11)(12)(13). Production of IgA, IgE, IgG, and IgM Abs has also been demonstrated (14,15).…”