Publications

Peer Reviewed Publications

1. Herbert DR, Lee JJ, Lee NA, Nolan TJ, Schad GA, Abraham D. Role of IL-5 in innate and adaptive immunity to larval Strongyloides stercoralis in mice. J Immunol. 2000 Oct 15; 165(8):4544-51.
2. Herbert DR, Nolan TJ, Schad GA, Lustigman S, Abraham D. Immunoaffinity-isolated antigens induce protective immunity against larval Strongyloides stercoralis in mice. Exp Parasitol. 2002 Feb; 100(2):112-20.
3. Herbert DR, Nolan TJ, Schad GA, Abraham D. The role of B cells in immunity against larval Strongyloides stercoralis in mice. Parasite Immunol. 2002 Feb; 24(2):95-101.
4. Kerepesi LA, Nolan TJ, Schad GA, Lustigman S, Herbert DR, Keiser PB, Nutman TB, Krolewiecki AJ, Abraham D. Human immunoglobulin G mediates protective immunity and identifies protective antigens against larval Strongyloides stercoralis in mice. J Infect Dis. 2004 Apr 1; 189(7):1282-90.
5. Herbert DR, Hölscher C, Mohrs M, Arendse B, Schwegmann A, Radwanska M, Leeto M, Kirsch R, Hall P, Mossmann H, Claussen B, Förster I, Brombacher F. Alternative macrophage activation is essential for survival during schistosomiasis and downmodulates T helper 1 responses and immunopathology. Immunity. 2004 May; 20(5):623-35.
6. Nieuwenhuizen N, Lopata AL, Jeebhay MF, Herbert DR, Robins TG, Brombacher F. Exposure to the fish parasite Anisakis causes allergic airway hyperreactivity and dermatitis. J Allergy Clin Immunol. 2006 May; 117(5):1098-105.
7. Leeto M, Herbert DR, Marillier R, Schwegmann A, Fick L, Brombacher F. TH1-dominant granulomatous pathology does not inhibit fibrosis or cause lethality during murine schistosomiasis. Am J Pathol. 2006 Nov; 169(5):1701-12.
8. Nieuwenhuizen N, Herbert DR, Lopata AL, Brombacher F. CD4+ T cell-specific deletion of IL-4 receptor alpha prevents ovalbumin-induced anaphylaxis by an IFN-gamma-dependent mechanism. J Immunol. 2007 Sep 1; 179(5):2758-65.
9. Herbert DR, Orekov T, Perkins C, Rothenberg ME, Finkelman FD. IL-4R alpha expression by bone marrow-derived cells is necessary and sufficient for host protection against acute schistosomiasis. J Immunol. 2008 Apr 1; 180(7):4948-55.
10. Herbert DR, Orekov T, Perkins C, Finkelman FD. IL-10 and TGF-beta redundantly protect against severe liver injury and mortality during acute schistosomiasis. J Immunol. 2008 Nov 15; 181(10):7214-20.
11. Khodoun M, Strait R, Orekov T, Hogan S, Karasuyama H, Herbert DR, Köhl J, Finkelman FD. Peanuts can contribute to anaphylactic shock by activating complement. J Allergy Clin Immunol. 2009 Feb; 123(2):342-51.
12. Morris SC, Heidorn SM, Herbert DR, Perkins C, Hildeman DA, Khodoun MV, Finkelman FD. Endogenously produced IL-4 nonredundantly stimulates CD8+ T cell proliferation. J Immunol. 2009 Feb 1; 182(3):1429-38.
13. Nieuwenhuizen N, Herbert DR, Brombacher F, Lopata AL. Differential requirements for interleukin (IL)-4 and IL-13 in protein contact dermatitis induced by Anisakis. Allergy. 2009 Sep; 64(9):1309-18.
14. O'Connell AE, Kerepesi LA, Vandergrift GL, Herbert DR, VAN Winkle TJ, Hooper DC, Pearce EJ, Abraham D. IL-4(-/-) mice with lethal Mesocestoides corti infections--reduced Th2 cytokines and alternatively activated macrophages. Parasite Immunol. 2009 Dec; 31(12):741-9.
15. Herbert DR, Yang JQ, Hogan SP, Groschwitz K, Khodoun M, Munitz A, Orekov T, Perkins C, Wang Q, Brombacher F, Urban JF, Rothenberg ME, Finkelman FD. Intestinal epithelial cell secretion of RELM-beta protects against gastrointestinal worm infection. J Exp Med. 2009 Dec 21; 206(13):2947-57.
16. Herbert DR, Orekov T, Roloson A, Ilies M, Perkins C, O'Brien W, Cederbaum S, Christianson DW, Zimmermann N, Rothenberg ME, Finkelman FD. Arginase I suppresses IL-12/IL-23p40-driven intestinal inflammation during acute schistosomiasis. J Immunol. 2010 Jun 1; 184(11):6438-46.
17. Rani R, Smulian AG, Greaves DR, Hogan SP, Herbert DR. TGF-ß limits IL-33 production and promotes the resolution of colitis through regulation of macrophage function. Eur J Immunol. 2011 Jul; 41(7):2000-9.
18. Butcher BA, Fox BA, Rommereim LM, Kim SG, Maurer KJ, Yarovinsky F, Herbert DR, Bzik DJ, Denkers EY. Toxoplasma gondii rhoptry kinase ROP16 activates STAT3 and STAT6 resulting in cytokine inhibition and arginase-1-dependent growth control. PLoS Pathog. 2011 Sep; 7(9):e1002236.
19. Wills-Karp M, Rani R, Dienger K, Lewkowich I, Fox JG, Perkins C, Lewis L, Finkelman FD, Smith DE, Bryce PJ, Kurt-Jones EA, Wang TC, Sivaprasad U, Hershey GK, Herbert DR. Trefoil factor 2 rapidly induces interleukin 33 to promote type 2 immunity during allergic asthma and hookworm infection. J Exp Med. 2012 Mar 12; 209(3):607-22.
20. Fu CL, Odegaard JI, Herbert DR, Hsieh MH. A novel mouse model of Schistosoma haematobium egg-induced immunopathology. PLoS Pathog. 2012; 8(3):e1002605. PMID: 22479181. PMCID: PMC3538196
21. Rani R, Jordan MB, Divanovic S, Herbert DR. IFN-gamma-Driven IDO Production from Macrophages Protects IL-4Ra-Deficient Mice against Lethality during Schistosoma mansoni Infection. Am J Pathol. 2012 May; 180(5):2001-8.
22. 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 Sep 15; 189(6):3078-84. PMID: 22896633. PMCID: PMC3432431
23. Fu, Chi-Ling, Odegaard, JI, Herbert, D.R., and Hsieh, M.H. A Novel Mouse Model of Schistosoma haematobium Egg-Induced ImmunopathologyPLoS Pathog.2012;8(3):e1002605. Epub 2012 Mar 29
24. Heitmann L, Rani R, Dawson L, Perkins C, Yang Y, Downey J, Hölscher C, Herbert DR. TGF-ß-responsive myeloid cells suppress type 2 immunity and emphysematous pathology after hookworm infection. Am J Pathol. 2012 Sep; 181(3):897-906. PMID: 22901754. PMCID: PMC3436937
25. McBerry C, Egan CE, Rani R, Yang Y, Wu D, Boespflug N, Boon L, Butcher B, Mirpuri J, Hogan SP, Denkers EY, Aliberti J, and Herbert, DR. Trefoil factor 2 negatively regulates Type 1 Immunity against Toxoplasma gondii J Immunol. 2012 Sep 15;189(6):3078-84.
26. Heitmann, L., Rani, R., Dawson, L, Perkins, C., Yang, Y., Downey, J., Holscher, C., Herbert, D.R. TGF-beta responsive myeloid cells suppress Type 2 Immunity and Emphysematous pathology after hookworm infection Am J Pathol. 2012 Sep;181(3):897-906
27. Hung LY, Lewkowich IP, Dawson LA, Downey J, Yang Y, Smith DE, Herbert DR.  IL-33 drives biphasic IL-13 production for noncanonical Type 2 immunity against hookworms Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):282-7.
28. Hung LY, Lewkowich IP, Dawson LA, Downey J, Yang Y, Smith DE, Herbert DR. IL-33 drives biphasic IL-13 production for noncanonical Type 2 immunity against hookworms. Proc Natl Acad Sci U S A. 2013 Jan 2; 110(1):282-7. PMID: 23248269. PMCID: PMC3315496
29. Licona-Limón P, Henao-Mejia J, Temann AU, Gagliani N, Licona-Limón I, Ishigame H, Hao L, Herbert DR, Flavell RA. Th9 Cells Drive Host Immunity against Gastrointestinal Worm Infection. Immunity. 2013 Oct 17; 39(4):744-57. PMID: 24138883. PMCID: PMC3881610
30. You D, Marr N, Saravia J, Shrestha B, Lee GI, Turvey SE, Brombacher F, Herbert DR, Cormier SA. IL-4Ra on CD4+ T cells plays a pathogenic role in respiratory syncytial virus reinfection in mice infected initially as neonates. J Leukoc Biol. 2013 Apr 9. PMID: 23543769
31. Gagliani N, Magnani CF, Huber S, Gianolini ME, Pala M, Licona-Limon P, Guo B, Herbert DR, Bulfone A, Trentini F, Di Serio C, Bacchetta R, Andreani M, Brockmann L, Gregori S, Flavell RA, Roncarolo MG. Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells. Nat Med. 2013 Apr 28. PMID: 23624599
32. McBerry C, Dias A, Shryock N, Lampe K, Gutierrez FR, Boon L, Herbert DR, Aliberti J. PD-1 modulates steady-state and infection-induced IL-10 production in vivo. Eur J Immunol. 2014 Feb; 44(2):469-79. PMID: 24165808. PMCID: PMC3955717
33. Apiwattanakul N, Thomas PG, Kuhn RE, Herbert DR, McCullers JA. Helminth infections predispose mice to pneumococcal pneumonia but not to other pneumonic pathogens. Med Microbiol Immunol. 2014 Oct; 203(5):357-64. PMID: 24952091. PMCID: PMC3315496
34. Hung LY, Sen D, Oswald EM, Oniskey TK, Wolters P, Kim CC, Krummel MF and Herbert DR.  Alveolar macrophages utilize Trefoil factor 2 for Wnt-mediated regeneration of damaged lung epithelia Submitted
35. Nieves W, Hung LY, Oniskey TK, Viollet B, Herbert DR.  Metabolic control of macrophage activation controls Type 2 immunity and pulmonary tissue repair  Submitted
36. Chan P, Carrera Silva E, Joannas LD, Hu D, Hunstmann S, Eng C, Licona-Limon P, Weinstein JS, Herbert DR, Craft JE, Flavell F, Torgerson DG, Burchard EG, and Rothlin CV Tyro3 is a Negative Regulator of Type 2 Immunity Submitted
37. Hung LY, Oniskey T, Sen D, Krummel M, Kim CC, and Herbert DR Trefoil factor 2 promotes epithelial repair and blocks injury-induced lung fibrosis Submitted

Research Program

     The Herbert lab is investigating how mucosal epithelia and macrophages function together to maintain and restore pulmonary function under steady-state and infectious conditions.  Our main project centers upon Trefoil factor proteins, a largely enigmatic family of mucosal cytokines, in controlling immunity at the mucosal interface.  Recent evidence shows that TFF proteins regulate members of the Wnt family of glycoprotein’s. Given the central role of Wnt’s in epithelial differentiation and regeneration, our work brings a clearer understanding of how Trefoil factor signaling controls barrier integrity through modulation of Wnt signaling. One of our most recent findings is that TFF2 is expressed within various macrophage populations of humans and mice and promotes a wound healing/M2 phenotype. Our generation of a novel co-culture system called the macrophage-epithelial repair assay (MERA), which uses primary tracheal epithelia and tissue macrophages has facilitated the discovery that TFF2 interfaces with the Wnt pathway to facilitate epithelial regeneration.

     

Our lab is also investigating how metabolic enzymes regulate host immunity against parasite infection.  This is because gastrointestinal (GI) nematodes exert profound metabolic demands upon their hosts, but how this affects immune cell function is entirely unclear. The hypothesis driving this project is that metabolic enzyme dysregulation favors chronic GI nematode infection.  We have generated mutant mice with either a cell-specific deletion or over-expression of the catalytic α subunit of adenosine monophosphate kinase (AMPK) a heterotrimeric enzyme complex of αβγ subunits that restores cellular energy. Recent data show that deletion of AMPK in alveolar macrophages disrupts host immunity and tissue repair during infection with the parasitic hookworm Nippostrongylus brasiliensis.   Hence, our laboratory is poised to gain unique insight(s) into the molecular mechanisms that govern the host-pathogen interface and mucosal immunity at barrier surfaces.

Significant Publications

1. 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.This manuscript provided the first formal demonstration of the biological importance of the M2 phenotype in vivo
   I designed and executed all experiments and analyses and co-wrote the manuscript.
2. 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. This manuscript provided the first clear demonstration that epithelial cell molecules can interfere with helminth survival in vivo.
   I designed and executed all experiments and analyses and co-wrote the manuscript.
3. Rani, R., Smulian, A.G., Greaves, D.R., Hogan, S.P., and Herbert, D.R.,TGF-beta limits colitis severity and promotes resolution through regulation of macrophage activation. European J Immunology. 2011 Jul;41 (7):2000-9. This manuscript showed that TGF-beta serves a non redundant role in macrophage biology that is critical for resolution of mucosal inflammation.
   I designed and executed all experiments and analyses and co-wrote the manuscript.
4. 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. This manuscript provided the first demonstration of a Trefoil factor protein that polarizes the innate immune response to allergens and helminthes
   I conceived the study, designed the experiments, performed the analyses, and wrote the manuscript.
5. Hung LY, Lewkowich IP, Dawson LA, Downey J, Yang Y, Smith DE, Herbert DR.  IL-33 drives biphasic IL-13 production for noncanonical Type 2 immunity against hookworms Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):282-7.  This manuscript provided the first demonstration that Type 2 memory responses driven by CD4+ TH2 and ILC2 populations within the hookworm damaged lung are IL-33 dependent.
   I conceived the study, designed the experiments, analyzed the data and wrote the manuscript.