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MBPhD Programme

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POLLARA, Gabriel

Entered:

2000

Current Position:

Qualified 2006

PhD title:

"Functional Effects of HSV Infection of Dendritic Cells"

Principal Supervisor:

Profs David Katz, Benny Chain

Funding Source:

George Mills Scholarship

Description of Project:

Dendritic cells (DC) are critical initiators of adaptive immune responses to herpes simplex virus-1 (HSV-1), and are likely to encounter the virus early after infection of skin or mucosa. We investigated the effects of HSV-1 infection on the function of DC. The direct effect of this interaction was to impair the ability of DC to stimulate T cell proliferation. However, HSV-1 infection of DC also resulted in activation of DC signalling and phenotype. This occurred both through viral glycoprotein interaction with DC and via type I interferon secretion after infection. These findings suggest the hypothesis that the coupling of viral entry to the activation of DC signalling pathways is counterbalanced by viral disruption of DC function, delaying the generation of immune responses to HSV-1. Current studies aim to elucidate the viral components responsible for this activation and inhibition.

PubMed-accessible Publications:

Bunyard,P., Handley,M., Pollara,G., Rutault,K., Wood,I., Chaudry,M., Alderman,C., Foreman,J., Katz,D.R., & Chain,B.M. (2003) Ribotoxic stress activates p38 and JNK kinases and modulates the antigen-presenting activity of dendritic cells. Mol.Immunol., 39, 815-827.

Rad,A.N., Pollara,G., Sohaib,S.M., Chiang,C., Chain,B.M., & Katz,D.R. (2003) The differential influence of allogeneic tumor cell death via DNA damage on dendritic cell maturation and antigen presentation. Cancer Res., 63, 5143-5150.

Pollara,G ., Katz,D.R., & Chain,B.M. (2004) The host response to herpes simplex virus infection. Curr.Opin.Infect.Dis., 17, 199-203.

Pollara,G ., Jones,M., Handley,M.E., Rajpopat,M., Kwan,A., Coffin,R.S., Foster,G., Chain,B., & Katz,D.R. (2004) Herpes simplex virus type-1-induced activation of myeloid dendritic cells: the roles of virus cell interaction and paracrine type I IFN secretion. J.Immunol., 173, 4108-4119.

Pollara,G ., Jones,M., Handley,M.E., Rajpopat,M., Kwan,A., Coffin,R.S., Foster,G., Chain,B., & Katz,D.R. (2004) Herpes simplex virus type-1-induced activation of myeloid dendritic cells: the roles of virus cell interaction and paracrine type I IFN secretion. J.Immunol., 173, 4108-4119.

Pollara,G ., Kwan,A., Newton,P.J., Handley,M.E., Chain,B.M., & Katz,D.R. (2005) Dendritic cells in viral pathogenesis: protective or defective? Int.J.Exp.Pathol., 86, 187-204.

Pachiadakis, I., Pollara,G., Chain,B.M., & Naoumov,N.V. (2005) Is hepatitis C virus infection of dendritic cells a mechanism facilitating viral persistence? Lancet Infect.Dis., 5, 296-304.

Pollara,G ., Kwan,A., Newton,P.J., Handley,M.E., Chain,B.M., & Katz,D.R. (2005) Dendritic cells in viral pathogenesis: protective or defective? Int.J.Exp.Pathol., 86, 187-204.

Pollara,G. , Speidel,K., Samady,L., Rajpopat,M., McGrath,Y., Ledermann,J., Coffin,R.S., Katz,D.R., & Chain,B. Herpes simplex virus infection of dendritic cells: balance among activation, inhibition, and immunity.

Pollara,G ., Katz,D.R., & Chain,B.M. (2005) LIGHTing up dendritic cell activation: Immune regulation and viral exploitation. J.Cell Physiol., 205, 161-162.

Handley,M.E., Thakker,M., Pollara,G., Chain,B.M., & Katz,D.R. (2005) JNK activation limits dendritic cell maturation in response to reactive oxygen species by the induction of apoptosis. Free Radic.Biol.Med. , 38, 1637-1652.

Handley,M.E., Pollara,G., Chain,B.M., & Katz,D.R. (2005) The use of targeted microbeads for quantitative analysis of the phagocytic properties of human monocyte-derived dendritic cells. J.Immunol.Methods., 297, 27-38.

Pollara,G. , Handley,M.E., Kwan,A., Chain,B.M., & Katz,D.R. (2006) Autocrine type I interferon amplifies dendritic cell responses to lipopolysaccharide via the nuclear factor-kappaB/p38 pathways. Scand.J.Immunol., 63, 151-154.

Swetman Andersen , C.A. , Handley,M., Pollara,G., Ridley,A.J., Katz,D.R., & Chain,B.M. (2006) beta1-Integrins determine the dendritic morphology which enhances DC-SIGN-mediated particle capture by dendritic cells. Int.Immunol., 18, 1295-1303.

Pollara,G ., Handley,M.E., Kwan,A., Chain,B.M., & Katz,D.R. (2006) Autocrine type I interferon amplifies dendritic cell responses to lipopolysaccharide via the nuclear factor-kappaB/p38 pathways. Scand.J.Immunol., 63, 151-154.

Reske,A., Pollara,G., Krummenacher,C., Chain,B.M., & Katz,D.R. (2007) Understanding HSV-1 entry glycoproteins. Rev.Med Virol., 17, 205-215.

Handley,M.E., Rasaiyaah,J., Barnett,J., Thakker,M., Pollara,G., Katz,D.R., & Chain,B.M. (2007) Expression and function of mixed lineage kinases in dendritic cells. Int.Immunol., 19, 923-933.