Mast cell-derived IL-10 protects intestinal barrier integrity during malaria in mice and regulates parasite transmission to with a female-biased immune response.

Malaria is strongly predisposed to bacteremia, which is associated with increased gastrointestinal permeability and a poor clinical prognosis. We previously identified mast cells (MCs) as mediators of intestinal permeability in malaria and described multiple cytokines that rise with parasitemia, including interleukin (IL)-10, which could protect the host from an inflammatory response and alter parasite transmission to mosquitoes. Here, we used the Cre-loxP system and non-lethal 17XNL to study the roles of MC-derived IL-10 in malaria immunity and transmission.

The Basophil IL-18 Receptor Precisely Regulates the Host Immune Response and Malaria-Induced Intestinal Permeability and Alters Parasite Transmission to Mosquitoes without Effect on Gametocytemia.

We have recently demonstrated that basophils are protective against intestinal permeability during malaria and contribute to reduced parasite transmission to mosquitoes. Given that IL-18 is an early cytokine/alarmin in malaria and has been shown to activate basophils, we sought to determine the role of the basophil IL-18R in this protective phenotype. To address this, we infected control [ or basoIL-18R (+)] mice and mice with basophils lacking the IL-18R [ × Basoph8 or basoIL-18R (-)] with 17XNL, a nonlethal strain of mouse malaria.

Basophil Depletion Alters Host Immunity, Intestinal Permeability, and Mammalian Host-to-Mosquito Transmission in Malaria.

Malaria-induced bacteremia has been shown to result from intestinal mast cell (MC) activation. The appearance of MCs in the ileum and increased intestinal permeability to enteric bacteria are preceded by an early Th2-biased host immune response to infection, characterized by the appearance of IL-4, IL-10, mast cell protease (Mcpt)1 and Mcpt4, and increased circulating basophils and eosinophils. Given the functional similarities of basophils and MCs in the context of allergic inflammation and the capacity of basophils to produce large amounts of IL-4, we sought to define the role of basophils in increased intestinal permeability, in MC influx, and in the development of bacteremia in the context of malaria.

Mast Cell Chymase/Mcpt4 Suppresses the Host Immune Response to , Limits Malaria-Associated Disruption of Intestinal Barrier Integrity and Reduces Parasite Transmission to .

An increase in mast cells (MCs) and MCs mediators has been observed in malaria-associated bacteremia, however, the role of these granulocytes in malarial immunity is poorly understood. Herein, we studied the role of mouse MC protease (Mcpt) 4, an ortholog of human MC chymase, in malaria-induced bacteremia using knockout () mice and C57BL/6J controls, and the non-lethal mouse parasite 17XNL. Significantly lower parasitemia was observed in mice compared with controls by day 10 post infection (PI).

A new mouse SNP genotyping assay for speed congenics: combining flexibility, affordability, and power.

Background: Speed congenics is an important tool for creating congenic mice to investigate gene functions, but current SNP genotyping methods for speed congenics are expensive. These methods usually rely on chip or array technologies, and a different assay must be developed for each backcross strain combination. "Next generation" high throughput DNA sequencing technologies have the potential to decrease cost and increase flexibility and power of speed congenics, but thus far have not been utilized for this purpose.