• Dennis Kasper
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What We Do

The focus of the Kasper laboratory is on the centrality of the microbiome in immune system development, maturation, and regulation. The laboratory’s research defines the phylogenetic diversity, immune mechanisms, and immunomodulatory therapeutic potential of bacteria and bacterial molecules in autoimmune and infectious diseases. We also investigate the chemistry and immunology of bacterial polysaccharides and lipids, gaining fundamental insights into their role in pathogenesis, as protective vaccine antigens, and as critical modulators of mucosal and systemic immunity.

Selected Recent Publications

Meng Wu and Dennis L Kasper. 2020. “When lab mice go wild, fungi are in play.” Cell Host Microbe, 27, 5, Pp. 687-688.Abstract
In this issue of Cell Host & Microbe, Yeung et al. (2020) and Lin et al. (2020) expose laboratory mice to a natural environment and use immune and microbiota characterization to show that fungi promote more human-like immunity. These studies will help develop animal models to more accurately resemble human immune responses.
Deepshika Ramanan, Esen Sefik, Silvia Galvin-Pena, Meng Wu, Liang Yang, Zhen Yang, Aleksandar Kostic, Tatyana Golovkina, Dennis L Kasper, Diane Mathis, and Christophe Benoist. 2020. “An immunologic mode of multigenerational transmission governs a gut Treg setpoint.” Cell, 181, 6, Pp. 1276-1290.Abstract

At the species level, immunity depends on the selection and transmission of protective components of the immune system. A microbe-induced population of RORg -expressing regulatory T cells (Tregs) is essential in controlling gut inflammation. We uncovered a non-genetic, non-epigenetic, non-microbial mode of transmission of their homeostatic setpoint. RORg+ Treg proportions varied between inbred mouse strains, a trait transmitted by the mother during a tight age window after birth but stable for life, resistant to many microbial or cellular perturbations, then further transferred by females for multiple generations. RORg+ Treg proportions negatively correlated with IgA production and coating of gut commensals, traits also subject to maternal transmission, in an immunoglobulin- and RORg+ Treg-dependent manner. We propose a model based on a double-negative feedback loop, vertically transmitted via the entero-mammary axis. This immunologicmode of multi-generational transmission may provide adaptability and modulate the genetic tuning of gut immune responses and inflammatory disease susceptibility.

Wen Zheng, Wenjing Zhao, Meng Wu, Xinyang Song, Florence Caro, Ximei Sun, Francesca Gazzaniga, Giuseppe Stefanetti, Sungwhan Oh, John J Mekalanos, and Dennis L Kasper. 2020. “Microbiota-targeted maternal antibodies protect neonates from enteric infection.” Nature, 577, 7791, Pp. 543-548.Abstract
Although maternal antibodies protect newborn babies from infection1,2, little is known about how protective antibodies are induced without prior pathogen exposure. Here we show that neonatal mice that lack the capacity to produce IgG are protected from infection with the enteric pathogen enterotoxigenic Escherichia coli by maternal natural IgG antibodies against enterotoxigenic E. coli when antibodies are delivered either across the placenta or through breast milk. By challenging pups that were fostered by either maternal antibody-sufficient or antibody-deficient dams, we found that breast-milk-derived IgG was critical for protection against mucosal disease induced by enterotoxigenic E. coli. IgG also provides protection against systemic infection by E. coli. Pups used the neonatal Fc receptor (FcRn) to transfer IgG from milk into serum. The maternal commensal microbiota can induce antibodies that recognize antigens expressed by enterotoxigenic E. coli and other Enterobacteriaceae species. Induction of maternal antibodies against a commensal Pantoea species confers protection against enterotoxigenic E. coli in pups. This role of the microbiota in eliciting protective antibodies to a specific neonatal pathogen represents an important host defence mechanism against infection in neonates.
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