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Introduction: The intestinal microbiota plays an important role in modulating host immune responses. Oral Toxoplasma gondii infection can promote intestinal inflammation in certain mice strains. The IDO-AhR axis may control tryptophan (Trp) metabolism constituting an important immune regulatory mechanism in inflammatory settings., Aims: In the present study, we investigated the role of the intestinal microbiota on Trp metabolism during oral infection with T gondii., Methods and Results: Mice were treated with antibiotics for four weeks and then infected with T gondii by gavage. Histopathology and immune responses were evaluated 8 days after infection. We found that depletion of intestinal microbiota by antibiotics contributed to resistance against T gondii infection and led to reduced expression of AhR on dendritic and Treg cells. Mice depleted of Gram-negative bacteria presented higher levels of systemic Trp, downregulation of AhR expression and increased resistance to infection whereas depletion of Gram-positive bacteria did not affect susceptibility or expression of AhR on immune cells., Conclusion: Our findings indicate that the intestinal microbiota can control Trp availability and provide a link between the AhR pathway and host-microbiota interaction in acute infection with T gondii., (© 2020 John Wiley & Sons Ltd.)

Background: The purpose of this study was to assess the effect of arginine supplementation on arginase activity, tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) synthesis in cultured splenic macrophages from a murine model of intestinal obstruction (IO). The effects of nitric oxide synthase (iNOS) inhibition were also studied using iNOS knockout animals., Material and Methods: Male C57BL6/J wild-type (WT) and iNOS knockout (iNOS-/-) mice were randomized into 6 groups: Sham and Sham-/- (standard chow), IO and IO-/- (standard chow + IO), and Arg and Arg-/- (standard chow supplemented with arginine + IO). After 7 days of treatment with standard or supplemented chow, IO was induced. Arginase activity as well as TNF-α and IL-10 levels were analyzed in splenic macrophage cultures., Results: Arginine supplementation and the absence of iNOS increased arginase activity in splenic macrophages (Arg, IO-/-, and Arg-/- groups vs the Sham group; P < .05). Arginine was also related to a decrease in TNF-α levels (Arg vs IO group, P < .05) and maintenance of IL-10 levels (Arg vs other groups, P > .05). The inhibition of iNOS did not result in effects on the concentration of cytokines (Sham-/-, IO-/-, and Arg-/- vs other, P < .05)., Conclusions: Arginine supplementation and iNOS inhibition led to increased arginase activity. Arginine availability decreased plasma TNF-α levels, which may be directly related to nitric oxide derived from arginine., (© 2014 American Society for Parenteral and Enteral Nutrition.)

Animals are colonized by their indigenous microbiota from the early days of life. The estimated number of associated bacterial cells in humans is around of 10(14) per individual, most of them in the gut. Several studies have investigated the microbiota-host relationship, and the use of germfree animals has been an important tool in these studies. These animals, when infected with a pathogen, have shown to be sometimes more resistant and other times more susceptible than conventional animals. Leishmaniasis is a worldwide public health problem and presents a spectrum of clinical manifestations. However, very few studies have addressed the role of the indigenous microbiota on the outcome of this disease. In this review, we will highlight and discuss the data available on the ways by which the microbiota can influence the outcome of the disease in murine experimental models of cutaneous infection with Leishmania., (© 2015 John Wiley & Sons Ltd.)

Leishmania (Viannia) braziliensis causes cutaneous and mucosal leishmaniasis in several countries in Latin America. In mammals, the parasites live as amastigotes, interacting with host immune cells and stimulating cytokine production that will drive the type of the specific immune responses. Generation of Th17 lymphocytes is associated with tissue destruction and depends on IL-1β, IL-6, TGF-β and IL-23 production, whereas IL-10 and TGF-β are associated with tissue protection. Here, we evaluate whether amastigotes stimulate peripheral blood mononuclear cells (PBMCs) from healthy donors to produce the major cytokines responsible for the generation of Th17. Seven L. (V.) braziliensis isolates from patients with different clinical forms of leishmaniasis were expanded in interferon-γ knockout mice to obtain amastigotes and in culture to get promastigotes. The parasites were used to stimulate PBMCs from healthy donors, and cytokine production was evaluated by ELISA or qPCR. Amastigotes and promastigotes induced IL-10 production in PBMCs; however, only amastigotes induced IL-1β, IL-6 and TGF-β. These data demonstrate for the first time that L. (V.) braziliensis amastigotes directly stimulate production of a unique pattern of cytokines that could contribute to the generation of Th17., (© 2014 John Wiley & Sons Ltd.)

Neutrophils are involved in the early stages of immune responses to pathogens. Here, we investigated the role of neutrophils during the establishment of Leishmania amazonensis infection in BALB/c and C57BL/6 mice. First, we showed an accumulation of neutrophils between 6 and 24 h post-infection, followed by a reduction in neutrophil numbers after 72 h. Next, we depleted neutrophils prior to infection using RB6-8C5 or 1A8 mAb. Neutrophil depletion led to faster lesion development, increased parasite numbers and higher arginase activity during the first week of infection in BALB/c mice, but not in C57BL/6 mice. Increased susceptibility was accompanied by augmented levels of anti-L. amazonensis IgG and increased production of IL-10 and IL-17. Because IL-10 is a mediator of susceptibility to Leishmania infection, we blocked IL-10 signalling in neutrophil-depleted mice using anti-IL-10R. Interestingly, inhibition of IL-10 signalling abrogated the increase in parasite loads observed in neutrophil-depleted mice, suggesting that parasite proliferation is at least partially mediated by IL-10. Additionally, we tested the effect of IL-17 in inflammatory macrophages and observed that IL-17 increased arginase activity and favoured parasite growth. Taken together, our data indicate that neutrophils control parasite numbers and limit lesion development during the first week of infection in BALB/c mice., (© 2013 John Wiley & Sons Ltd.)

Leishmaniasis causes high morbidity and mortality in tropical and subtropical areas. Mast cells can be activated by Leishmania or Leishmania products in vitro and in vivo. Several innate immunity mediators, including some released by mast cells, play roles in the outcome of the disease. In this study, we examined whether pharmacological inactivation of mast cells before infection with L. major interferes with the progressive disease in BALB/c mice. The results show that, when mast cells are degranulated before challenge with L. major, susceptible mice become more resistant to infection, as measured by decrease of lesion size and lower parasite loads. Mast cell degranulation reduced IL-4 production. Moreover, mast cells degranulation enhanced mRNA expression for IFN-gamma, inducible nitric oxide, CCL2 and CCL5 in response to infection. Mast cell degranulation also decreased parasite loads in IL-4 KO animals, indicating that mediators other than IL-4 are involved in susceptibility in vivo. Taken together, our results disclose a role for mast cells in the induction of susceptibility to infection. This work contributes to a better understanding of the role of mast cells in Leishmania infection, and suggests a new field of study for strategies to contain the parasite, restricting its dissemination.

In the present work, the development of experimental leishmaniasis was examined in sensitized BALB/c mice that were chronically fed with antigen. After an oral challenge with egg white solution, the ovalbumin (Ova)-sensitized mice showed an increase in serum anti-Ova IgE and IgG1 antibodies. Lesions induced by Leishmania major infection were reduced by the ingestion of Ova in sensitized mice, as assessed by reduced footpad growth, lower parasite loads and improved pathological outcome compared to sham sensitized mice. Moreover, such findings were connected to a shift to a Th1 response involving higher IFN-gamma production and serum levels of IgG2a anti-Leishmania antigens. The data appear to corroborate the suggestion that chronic ingestion of an antigen by sensitized mice modulates the immunological system through a shift in cytokine release, exhibiting a healing response and resistance to L. major infection.

During in vitro transformation of Schistosoma mansoni cercariae into schistosomula, surface and glandular materials are released into the culture medium. Extracts of these materials, termed cercarial released extracts 1 and 2 (CRE-1 and CRE-2), were analysed and found to consist primarily of protein and carbohydrate at ratios of 5:1 (CRE-1) and 7:1 (CRE-2). It was observed that inclusion of either CRE-1 or CRE-2 in cultures of human peripheral blood mononuclear cells (PBMN) led to decreased cell proliferation. This was true whether the cells were resting, control cultures or were stimulated with either phytohaemagglutinin or an antigenic preparation from adult S. mansoni worms. The inhibition was equally effective with PBMN of patients with active schistosomal infection or PBMN from uninfected individuals. Since these materials are released spontaneously during cercarial-to-schistosomular transformation they may have a putative immunosuppressive effect in decreasing antischistosomular activities early after cercarial penetration.