A mouse protozoan boosts antigen-specific mucosal IgA responses in a specific lipid metabolism- and signaling-dependent manner.

IgA antibodies play an important role in mucosal immunity. However, there is still no effective way to consistently boost mucosal IgA responses, and the factors influencing these responses are not fully understood. We observed that colonization with the murine intestinal symbiotic protozoan Tritrichomonas musculis (T.mu) boosted antigen-specific mucosal IgA responses in wild-type C57BL/6 mice. This enhancement was attributed to the accumulation of free arachidonic acid (ARA) in the intestinal lumen, which served as a signal to stimulate the production of antigen-specific mucosal IgA. When ARA was prevented from undergoing its downstream metabolic transformation using the 5-lipoxygenase inhibitor zileuton or by blocking its downstream biological signaling through genetic deletion of the Leukotriene B4 receptor 1 (Blt1), the T.mu-mediated enhancement of antigen-specific mucosal IgA production was suppressed. Moreover, both T.mu transfer and dietary supplementation of ARA augmented the efficacy of an oral vaccine against Salmonella infection, with this effect being dependent on Blt1. Our findings elucidate a tripartite circuit linking nutrients from the diet or intestinal microbiota, host lipid metabolism, and the mucosal humoral immune response.

Fam96a is essential for the host control of Toxoplasma gondii infection by fine-tuning macrophage polarization via an iron-dependent mechanism.

BACKGROUND: Toxoplasmosis affects a quarter of the world's population. Toxoplasma gondii (T.gondii) is an intracellular parasitic protozoa. Macrophages are necessary for proliferation and spread of T.gondii by regulating immunity and metabolism. Family with sequence similarity 96A (Fam96a; formally named Ciao2a) is an evolutionarily conserved protein that is highly expressed in macrophages, but whether it play a role in control of T. gondii infection is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we utilized myeloid cell-specific knockout mice to test its role in anti-T. gondii immunity. The results showed that myeloid cell-specific deletion of Fam96a led to exacerbate both acute and chronic toxoplasmosis after exposure to T. gondii. This was related to a defectively reprogrammed polarization in Fam96a-deficient macrophages inhibited the induction of immune effector molecules, including iNOS, by suppressing interferon/STAT1 signaling. Fam96a regulated macrophage polarization process was in part dependent on its ability to fine-tuning intracellular iron (Fe) homeostasis in response to inflammatory stimuli. In addition, Fam96a regulated the mitochondrial oxidative phosphorylation or related events that involved in control of T. gondii. CONCLUSIONS/SIGNIFICANCE: All these findings suggest that Fam96a ablation in macrophages disrupts iron homeostasis and inhibits immune effector molecules, which may aggravate both acute and chronic toxoplasmosis. It highlights that Fam96a may autonomously act as a critical gatekeeper of T. gondii control in macrophages.

Characterization of an EPS-producing bifidobacterial strain based on integration of phenotypic and complete genome sequencing data.

Bifidobacterium and Lactobacillus are known to be common members of the human intestinal microbiota, which play important roles in maintaining the homeostasis of host gut microenvironment. Several bifidobacterial and lactobacilli strains have been used as probiotics for health benefits. The exopolysaccharides (EPSs) produced by strains from Bifidobacterium and Lactobacillus are considered as beneficial traits mediating these beneficial effects. In this study, 21 strains belonging to Bifidobacterium and Lactobacillus were isolated from healthy infants' stool and were screened for EPS-producing ability. Among these strains, Bifidobacterium longum XZM1 showed the highest EPS productivity, which was further confirmed and characterized. The complete genome of strain XZM1 was sequenced, which revealed the presence of a gene cluster for EPS production. Furthermore, comparative genome analysis was performed among XZM1 and other strains from B. longum species. Following purification, the molecular weight (Mw) of EPS from XZM1 was determined as 4023 Da (Mw) through gel permeation chromatography. Analysis of the EPS hydrolysates revealed that the EPS was composed of mannose, glucose, galactose, arabinose, and fucose. Additionally, the EPS exhibited higher scavenging abilities toward hydroxyl than 1,1-diphenyl-2-picrylhydrazyl free radical. Overall, these results suggest that XZM1 from B. longum species may be a promising probiotic candidate.