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New Scholar Award in Global Infectious Disease
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Jatin M.
Vyas,
M.D., Ph.D.
Massachusetts General Hospital
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Antigen Processing and Presentation in the Specialized Enterocyte, M Cell
Mucosal surfaces represent the interface between host and environment. The
gastrointestinal and respiratory tracts extract nutrients from the lumen; however numerous
pathogens exist in this milieu that must be excluded. As the first line of defense, copious
mucous formation in the respiratory tract serves as a non-specific physical barrier between
alveolar cells and microorganisms. The glycocalyx on the mucosal brush border provides an
additional non-specific barrier mechanism to prevent attachment of pathogens to the
absorbing enterocyte. Additionally, tight junctions between cells prevent non-specific
absorption of macromolecules and prevent migration of bacteria and viruses to deeper
structures. However, these defenses are incomplete. To augment them, B cells secrete
immunoglobulins in large quantities into the lumen to bind specific antigenic epitopes on
the pathogen’s cell surface and thwart infection. To combat host defense mechanisms,
pathogens have devised specific mechanisms to subvert this system and invade the mucosal
lining. Hence, a specific immune response must be generated to contain infection. The
ability to mount a quick and effective cellular response to these pathogens is the hallmark
of an effective immune system.
In contrast to B cells, T lymphocytes do not recognize whole foreign proteins, but rather
degraded proteins called peptides in association with major histocompatibility complex
(MHC) class I or II molecules. Thus, cells must lie at the mucosal interface that possess the
capacity to degrade foreign proteins, create peptides and display them with MHC class I
and II molecules on the cell surface. One such candidate cell, the microfold (or M) cell,
differs from other cells on the intestinal lining (enterocytes). These cells lack the thick
glycocalyx at the apical membrane. M cells constitutively absorb contents of the lumen to
sample the environment. Early studies demonstrated that M cells display MHC class I and
II molecules on the cell surface. Moreover, T cells lie in deep invaginations of the
basolateral surfaces of M cells making close contact. While current knowledge about the
antigen processing and presenting functions of M cells is lacking, it is clear that M cells
play a central role in the pathogenesis of many diverse infectious agents including
Salmonella typhimurium, Mycobacterium tuberculosis and reovirus. The goal of my work
is to determine the rules that govern antigen processing and presentation in M cells. Further
insights into the functions of M cells will likely have a significant impact on the
understanding of mucosal immunity and lead to novel forms of oral vaccines targeted to M
cells.
Contact
Dr. Vyas.
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