Member of the Graduate Groups of Microbiology, Immunology, and Comparative Pathology

Research Interests

Our research focuses on the question: How are some pathogens able to cause persistent infections, despite induction of an immune response? We are using the bacterial pathogen Brucella abortus to study this topic. B. abortus causes a febrile illness in humans, and if inappropriately treated, bacteria can persist for years in tissues such as liver, spleen and bone marrow. We are currently studying two aspects of B. abortus-host interactions that contribute to chronic infection: (1) A virulence factor called the Type IV secretion system that allows Brucella to survive intracelllularly in tissues of the reticuloendothelial system by injecting proteins into infected macrophages, and (2) Evasion of innate immune surveillance by Toll-like receptors and cytosolic pattern recognition receptors through production of “stealth” versions of pathogen-associated molecular patterns.

Our laboratory uses bacterial genetics and molecular biology techniques to characterize the function of the Type IV secretion system in Brucella. We are using macrophage and animal models and immunological techniques to dissect the interactions between the bacterium and host cells. By defining molecular interactions between bacteria and host cells, we will also learn how these interactions can be disrupted to develop better vaccines and treatments for chronic bacterial infections.

Recent publications

A. B. den Hartigh, H.G. Rolán, M.F. de Jong, and R.M. Tsolis. 2008. Non-polar deletions of the Brucella virB operon reveal differential requirements for persistent infection. In press, Journal of Bacteriology.

Rolán, H.G. and R.M. Tsolis. 2008. Inactivation of the Type IV secretion system reduces the Th1 polarization of the immune response to Brucella abortus infection. In press, Infection and Immunity

Carvalho Neta, A.V., A.P.R. Steynen, T.A. Paixão, K.L. Miranda, F.L. Silva, C.M. Roux, R.M. Tsolis, H.A. Lewin, L.G. Adams, A.F. Carvalho, A.P. Lage, and R.L. Santos. 2008. Modulation of trophoblastic immune response by Brucella abortus. Infect. Immun. 76:1897-1907.

Rolán, H.G., A.B. den Hartigh, M. Kahl-McDonagh, T.A. Ficht, L.G. Adams and R.M. Tsolis. 2008. VirB12 is a serological marker of Brucella infection in experimental and natural hosts. Clin. Vaccine Immunol. 15208-214.

Godinez, I., T. Haneda, M. Raffatellu, M.D. George, T.A. Paixão, H.G. Rolán, R.L. Santos, S. Dandekar, R.M. Tsolis and A.J. Bäumler. 2008. T cells help to amplify inflammatory responses induced by Salmonella enterica serotype Typhimurium in the intestinal mucosa. Infect. Immun. 76:2008-2017.

Rolán, H.G. and R. M. Tsolis. 2007. Mice lacking components of adaptive immunity permit increased colonization levels of a Brucella abortus virB mutant. Infect. Immun. 75: 2965-73.

Sun, Y.-H., H.G. Rolán and R.M. Tsolis. 2007. Injection of flagellin into the host cell cytosol by Salmonella enterica serotype Typhimurium. J. Biol. Chem. 282:33897-901.

Roux, C.M., Rolan, H.G., Santos, R.L., Beremand, P.D., Thomas, T.L., Adams, L.G. and R.M. Tsolis. 2007. Brucella requires a functional Type IV secretion system to elicit innate immune responses in mice. Cell. Microbiol, 9:1851-69.

Kahl-McDonagh, M., Elzer, P.H., Hagius, S.D., Walker, J.V., Perry, Q.L., Seabury, C.M., den Hartigh, A.B., Tsolis, R.M., Adams, L.G. and T.A. Ficht. 2006. Evaluation of novel Brucella melitensis unmarked deletion mutants for safety and efficacy in the goat model of brucellosis.  Vaccine 24:5169-5177

Roux, C.M., Booth, N.J., Bellaire, B.H., Gee, J.M., Roop, R.M. II, Kovach, M.E., Tsolis, R.M., Elzer, P.H., and D.G. Ennis. 2006. RecA and RadA proteins of Brucella abortus do not perform overlapping protective DNA repair functions following oxidative burst. J. Bacteriol. 188:5187-5195.