Biology subjects

Saraav, I.

Publications and source records attributed to Saraav, I..

2 recordsLinked to original sources

bioRxiv2025

Early-life infection with Cryptosporidium parvum induces inflammatory responses to dietary antigens

To examine the effect of early-life infection with Cryptosporidium parvum on the development of oral tolerance, we developed a low-dose infection model in neonatal mice. C. parvum infection in neonatal mice results in immunopathology in the colon. IL-1{beta} released during C. parvum infection blocked the formation of colonic goblet cell associated antigen passages, which normally serve as a conduit for antigen uptake and development of peripheral regulatory T cells (pTregs), responsible for long-term oral tolerance. Following infection with C. parvum, adoptively transferred OT-II cells, which respond to ovalbumin (ova), developed reduced frequency of Foxp3+Ror{gamma}t+ cells in mesenteric lymph nodes with an expansion of TH1-like Tregs in the colon. The altered pTreg profile was accompanied by a strong TH1 immune response and robust IgG2c antibody responses to orally administered ova. Our findings suggest that intestinal inflammation and altered pTreg development leads to loss of oral tolerance during early life infection with C. parvum.

microbiology↗

bioRxiv2023

Cryptosporidium infection of human small intestinal epithelial cells induces type III interferon and impairs infectivity of Rotavirus.

Cryptosporidiosis is a major cause of severe diarrheal disease in infants from resource poor settings. The majority of infections are caused by the human-specific pathogen C. hominis and absence of in vitro growth platforms has limited our understanding of host-pathogen interactions and development of effective treatments. To address this problem, we developed a stem cell-derived culture system for C. hominis using human enterocytes differentiated under air-liquid interface (ALI) conditions. Human ALI cultures supported robust growth and complete development of C. hominis in vitro including all life cycle stages. C. hominis infection induced a strong interferon response from enterocytes, likely driven by an endogenous dsRNA virus in the parasite. Prior infection with Cryptosporidium induced type III IFN secretion and consequently blunted infection with Rotavirus, including live attenuated vaccine strains. The development of hALI provides a platform for further studies on human-specific pathogens, including clinically important coinfections that may alter vaccine efficacy.

microbiology↗