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Nicholas J. Mantis, Ph.D.

  • Nicholas J. Mantis, Ph.D.

    Nicholas J. Mantis, Ph.D.

    • Mucosal Immunology
    • Associate Professor and Chair, Department of Biomedical Sciences, School of Public Health

    • Ph.D., Cornell University (1994)
    • Postdoctoral training: Pasteur Institute (Paris)
    • Postdoctoral training: Children's Hospital Boston
    • Postdoctoral training: Harvard Medical School

  • The mucosal immune system produces secretory IgA antibodies that protect epithelial surfaces from toxins and microbial patho
    The mucosal immune system produces secretory IgA antibodies that protect epithelial surfaces from toxins and microbial pathogens

Research Interests

For the vast majority of microbial pathogens, the first encounter with a host occurs on the mucosal surfaces of the respiratory, genital or gastrointestinal tracts. Once contact has been initiated, there ensues a complex molecular interplay between the host and microbe that ultimately determines the success or failure of the infection process. Nowhere is the battle between host and microbe more intense than on the epithelial surfaces of the gastrointestinal tract. Enteric pathogens, such as Salmonella typhimuriumShigella flexneriE.coli O157:H7, and Vibrio cholerae, secrete a panoply of molecular "weapons", including toxins, that enable them to adhere to, colonize, and invade intestinal epithelial cells. To defend itself against these invaders, the intestinal epithelium is aligned closely with the innate and adaptive immune systems. The innate immune system consists of broadly reactive and relatively non-specific barriers to infection, including antimicrobial peptides, proteases, and mucus, that deter (but rarely prevent) bacterial attachment to epithelial cells surfaces. The adaptive immune response, on the other hand, is exquisitely more sophisticated, responding to infection through the local production and transport onto epithelial surfaces of secretory IgA (SIgA) antibodies capable of neutralizing even the most potent microbial pathogens and toxins.

Research in my laboratory is aimed at understanding how SIgA, alone and in combination with other components of the innate and adaptive immune systems, disarms microbial pathogens and neutralizes toxins on the mucosal surfaces of the gastrointestinal tract. We study S.typhimurium and S.flexneri as model enteroinvasive pathogens, and are particularly interested in the effects of anti-LPS IgA antibodies on bacterial colonization, attachment and invasion. Another focus of my laboratory is ricin, an extremely potent member of the shiga family of toxins that is considered a potential bioterrorism agent. Using cell culture and mouse models of ricin intoxication, we are investigating the mechanisms by IgA and IgG antibodies neutralize ricin in both mucosal and systemic compartments. Ultimately, the results from these studies will be applied to the development of much needed mucosal vaccines and therapeutics against naturally acquired infections and potential bioterrorism agents.

Select Publications

De Jesus M, Rodriguez AE, Yagita H, Ostroff GR, Mantis NJ.
Sampling of Candida albicans and Candida tropicalis by Langerin-positive dendritic cells in mouse Peyer's patches.
Immunology Letters.
(2015)
168
(1):
64-72.
Levinson KJ, De Jesus M, Mantis, NJ.
Rapid effects of a protective O-polysaccharide-specific monoclonal IgA on Vibrio cholerae agglutination, motility, and surface morphology.
Infect Immun.
(2015)
83
(4):
1674-1683.
Vance DJ, Rong Y, Brey RN 3rd, Mantis NJ.
Combination of two candidate subunit vaccine antigens elicits protective immunity to ricin and anthrax toxin in mice.
Vaccine.
(2015)
33
(3):
417-421.
Sully EK, Whaley KJ, Bohorova N, Bohorov O, Goodman C, Kim do H, Pauly MH, Velasco J, Hiatt E, Morton J, Swope K, Roy CJ, Zeitlin L, Mantis NJ.
Chimeric plantibody passively protects mice against aerosolized ricin challenge.
Clin Vaccine Immunol.
(2014)
21
(5):
777-782.
Rudolph MJ, Vance DJ, Cheung J, Franklin MC, Burshteyn F, Cassidy MS, Gary EN, Herrera C, Shoemaker CB, Mantis NJ.
Crystal structures of ricin toxin's enzymatic subunit (RTA) in complex with neutralizing and non-neutralizing single-chain antibodies.
J Mol Biol.
(2014)
426
(17):
3057-3068.