Research Overview

The Chlamydia Research Group has maintained an active and funded research program on the study of chlamydial infections for the last 30 years. During this time, the program initially developed and characterized the guinea pig and mouse models for chlamydial genital infection and subsequently employed those models to describe the basic adaptive immune mechanisms elicited by the infection. Their studies established an essential role for both antibody and cellular immune mechanisms in resolution of and resistance to genital disease and characterized those responses in the genital tract. While the vast majority of that work investigated the responses in the female, the laboratory has initiated and is conducting studies on the host response to chlamydial infection in the male genital tract. In addition, it is apparent that infection acquired by the female from the male by sexual transmission results in a shorter infection course, suggesting that there are factors involved in the male which can affect the response in the female.

While the host response is involved in a protective immune response, it is also patently clear that chlamydial disease is also caused by the host response. The current hypothesis is that both the acute inflammatory response and the T cell response play important roles in the production of disease. Therefore, the major goal of the research program currently is to understand the basic mechanisms of disease in both the genital tract and eye.

Using their animal models, the Chlamydia Research Group now has the ability to examine and define the molecular and cellular mechanisms in vivo that are initiated by infection and lead to the overall pathologic response. They have found that neutrophils enter the infected epithelium within 6 hours of infection, well before the organism has completed one cycle of replication, which takes about 24 hours. Currently, they are using molecular and cellular techniques to define the molecular mechanisms by which chlamydiae initiate the production of chemokines which result in the production of the inflammatory reaction. They are also examining the exact cellular and molecular mechanisms by which neutrophils damage the local epithelium and how they may influence the development of the adaptive immune response, all within the first 24 hours of infection. These studies will lead to exciting new concepts on the host-pathogen interaction at its most basic level.

Key Publications*

Rank, R.G., Bowlin, A.K., Reed, R., Darville, T. Characterization of chlamydial genital infection resulting from sexual transmission from male to female guinea pigs and determination of infectious dose. Infect. Immun., 71:6148-6154, 2003.

Nagarajan, U. M., O’Connell, C., Rank, R.G. Molecular characterization of guinea pig (Cavia porcellus) CD8a and CD8b cDNA. Tissue Antigens 63:184-189, 2004.

Nagarajan, U.M., Ojcius, D.M., Stahl, L., Rank, R.G., Darville, T. Chlamydia trachomatis induces expression of IFN-{gamma}-inducible protein10 and IFN-{beta} Independent of TLR2 and TLR4, but Largely Dependent on MyD88. J. Immunol.175: 450-460, 2005.

Liu, Z., Rank, R., Kaltenboeck, B., Magnino, S., Dean, D., Burall, L., Plaut, R.D., Read, T.D., Myers, G., and Bavoil, P.M.. Genomic plasticity of the rrn-nqrF intergenic segment in the Chlamydiaceae. The Journal of Bacteriology 189 (5):2128-2132, 2007.

Burall, L.S., Liu, Z., Rank, R., Bavoil, P.M. The chlamydial invasion-like protein gene conundrum. Microbes and Infection 9: 873-880, 2007.

Perfettini, J-L., Ojcius, D.M., Andrews, C.W., Korsmeyer, S.J., Rank, R.G., Darville, T. Role of proapoptotic BAX in propagation of Chlamydia muridarum (the mouse pneumonitis strain of Chlamydia trachomatis) and the host inflammatory response. J. Biol. Chem. 278: 9496-9502, 2003.

Rank, R.G. The CD4 Response. In Chlamydia: Genomics, Pathogenesis and Implications for Control, Bavoil, P. and Wyrick, P. (eds). Horizon Bioscience, Norfolk, U.K. 2006.

Rank, R.G. Chlamydial diseases. In The mouse in biomedical research, second edition, volume 2: Diseases. Fox, J.G., Newcomer, C., Smith, A., Barthold, S., Quimby, F., Davisson, M. (eds). Elsevier Inc., San Diego. pp. 325-348, 2007.

*To find additional publications by this author, please visit Pubmed Central, a National Institutes of Health-operated site for electronic distribution of life sciences research reports.

Research Support

Host response to Chlamydia genital infection in the male. 1R01 AI059650-01 NIAID, NIH; 12/01/04 – 11/30/08; Principal Investigator.