De'Broski R. Herbert, PhD
Infection and inflammation are unavoidable during the human experience. Thus, mechanisms that govern immunity and tissue repair dictate the balance between health and disease. The Herbert laboratory investigates the cellular and molecular mechanisms of parasitic helminth infection to gain insight into Type 2 immunity and the immunoregulatory/suppressive mechanisms of mucosal “wound healing” cascades.
Our studies in gene-targeted mice have demonstrated a critical role for interleukin 4/13 dependent effector mechanisms in macrophages and epithelia in host protection against parasitic worms. Using conditional deletion mutants, we are studying how the products of alternatively activated macrophages control infection outcome. Ongoing projects seek to understand how cell-specific deletion of metabolic regulators controls host protection and tissue immunopathology.
In addition, we investigate how mucosal tissue repair proteins within the Trefoil factor family (TFF1, TFF2, TFF3) exert immunoregulatory effects upon innate and adaptive immune cells during homeostasis and parasite infection within the pulmonary and gastrointestinal tract. We have shown that TFF2 drives Type 2 immunity through inducing the production of interleukin 33 from macrophages and inflammatory dendritic cells during hookworm infection. Moreover, TFF2 deficiency impairs mucosal barrier function, which augments steady-state Type 1 inflammation in the gastrointestinal tract and prevents protozoan infection. Ongoing projects will address the regulation of Trefoil proteins and their impact upon the human immune system. 
Selected Publications
Herbert, D. R., Hölscher, C., Mohrs, M., Arendse, B., Schwegmann, A., Radwanska, M., Leeto, M., Kirsch, R., Hall, P., Mossmann, H., Claussen, B., Förster, I. and Brombacher, F. “Alternative macrophages are essential for down-modulation of Type 1 responses, immunopathology, and survival during schistosomiasis” Immunity 2004 20(5): 623-351.
Herbert, D.R., Hogan, S.P., Groshwitz, K., Orekov, T., Perkins, C., Wang, J.Q., Wang, Q., Urban, J.F., Jr., Rothenberg, M.E., and Finkelman, F.D. “Intestinal epithelial cell secretion of RELM beta protects against gastrointestinal worm infection” Journal of Experimental Medicine. 2009 Dec 21;206 (13):2947-57
Herbert, D.R., Orekov, T., Perkins, C., Rothenberg, M.E., and Finkelman, F.D. “Arginase I suppresses IL-12/IL-23p40-driven intestinal inflammation during acute schistosomiasis” J Immunol. 2010 Jun 1;184 (11):6438-46.
Rani R, Smulian AG, Greaves DR, Hogan SP, Herbert DR. TGF-b limits IL-33 production and promotes the resolution of colitis through regulation of macrophage function Eur J Immunol. 2011 Jul;41(7):2000-9
Wills-Karp, M., Rani, R., Dienger, K., Lewkowich, I., Fox, J., Perkins, C., Lewis, L., Finkelman, F.D., Smith, D.E., Bryce, P.J., Curt-Jones, E., Wang, T., Sivaprasad, U., Hershey, G.K., and Herbert, D.R., “Trefoil factor 2 rapidly induces IL-33 to promote Type 2 immunity during allergic asthma and hookworm infection” Journal of Experimental Medicine 2012 Mar 12;209(3):607-22.
Heitmann L, Rani R, Dawson L, Perkins C, Yang Y, Downey J, Hölscher C, Herbert DR., “TGF-b responsive myeloid cells suppress Type 2 immunity and emphysematous pathology after Hookworm infection” Am J Pathol. 2012 Sep;181(3):897-906.
McBerry C, Egan CE, Rani R, Yang Y, Wu D, Boespflug N, Boon L, Butcher B, Mirpuri J, Hogan SP, Denkers EY, Aliberti J, Herbert DR., “Trefoil Factor 2 negatively regulates Type 1 immunity against Toxoplasma gondii” J Immunol. 2012 Aug 15.