Microbiology & Immunology Faculty
Peter H. Dube, Ph.D.
The research in the Dube laboratory is focused on inflammation and how inflammation leads to disease. In particular, we investigate how bacterial pathogens and their products influence inflammatory responses. The three major areas of interest are pulmonary infections leading to asthma or the exacerbation of asthma, acute infections of the lungs by biodefense-related pathogens and infectious gastroenteritis caused by invasive bacterial pathogens.
Our interests in asthma revolve around Mycoplasma pneumoniae and a toxin produced by this pathogen called the Community Acquired Respiratory Distress Syndrome toxin (CARDS toxin). Mycoplasma pneumoniae is often associated with acute exacerbations of asthma in children and adults and recent data suggests that CARDS toxin might be linked to a subset of asthma exacerbations. We are currently investigating how the CARDS toxin influences the immune system to promote asthma-like responses. Using a variety of animal models we have been able to show that exposure to purified CARDS toxin or low dose infection with M. pneumoiniae leads to the development of asthma-like inflammation in naive animals or exacerbation of asthma-like inflammation in animals with experimental asthma. We are using these models to dissect the immunological mechanisms responsible for generation of M. pneumoniae and CARDS toxin-associated asthma responses.
In addition to studying asthma we are also interested in understanding the acute pneumonia that develops during pneumonic plague (pulmonary infection with Yersinia pestis). Pneumonic plague is one of the most feared infections because it rapidly leads to death. We have discovered that one of the mechanisms used by Y. pestis to cause such an aggressive pneumonia is that inflammatory responses are blocked for the first 24hrs following initial infection. This delay in the inflammatory response provides a significant advantage to the pathogens. Studies investigate the virulence factors responsible for this delay in inflammatory responses.
Our interests in invasive bacterial pathogens of the gut are directed at understanding how Yersinia enterocolitica, a common food borne pathogen, avoids initial recognition and inflammatory responses. We are investigating the bacterial factors responsible for both activating and inhibiting the inflammasome. The inflammasome is the cellular machinery responsible for generating inflammatory responses and Y. enterocolitica regulates these responses at various stages. An important aspect of Y. enterocolitica virulence is the ability to elaborate a Type Three Secretion System (TTSS). TTSS allow bacterial pathogens to directly inject virulence factors into the host cell cytoplasm. We are interested in bacterial factors that make the cell permissive for performing TTS as these represent a novel group of virulence proteins that could be targeted for therapeutic intervention.
Biodefense research: We have initiated studies looking at the host response to Yersinia pestis infection. Y. pestis is the causative agent of plague. We employ models of both bubonic and primary pneumonic plague to look at gene expression in response to infection.
Medina, J.L., Coalson, J.J., Brooks, E.G., Winter, V.T., Chaparro, A., Principe, M.,Kannan, T.R., Baseman, J.B., and Peter H. Dube. 2012. Mycoplasma pneumoniae CARDS toxin induces pulmonary eosinophilic and lymphocytic inflammation. Am J Respir Cell Mol Biol (In press).
Hardy, R.D., Coalson,J.J., Peters, J.,Chapparo, A., Cantwell, A.M., Kannan, T.R., Baseman, J.B., and Dube, P.H. 2009. Analysis of pulmonary inflammation and function in the mouse and baboon after exposure to Mycoplasma pneumoniae CARDS toxin. Plos one. 4:e7562. PMID: 19859545
Zhong, Y., Cantwell, A.M., and Dube, P.H. 2010. Transforming growth factor-beta and CD-25 is important for controlling systemic dissemination following Yersinia enterocolitica infection. Infect and Immun. 78:3716-3725 PMID: 20584975
Xiaoyun Zhang, Gao, L., Lei L., Zhong, Y., Dube, P., Berton, M., Arulanandam, B., Zhang, J., and Zhong, G. 2009. A MyD88-dependent early IL-17 production protects mice against airway infection with the obligate intracellular pathogen Chlamydia muridarum. J. Immunol. 183:1291-1300 PMID: 19542374
Stacy, S., Pasquali, A., Sexton, V.L., Cantwell, A.M., Kraig, E, and Dube, P.H. 2008. An age-old paradigm challenged: old baboons generate vigorous humoral immune responses to LcrV, a plague antigen. J. Immunol. 181 (1):109-115 PMID: 18566375
Bose, R., Thinwa, J., Chaparro, A., Zhong, Y., Zhong., G, Bose, S., and Dube, P.H., 2011. MAP-kinase-dependent IL-1alpha intracrine signaling is modulated by YopP during Y. enterocolitica infection. Infect and Immun. In Press PMID: 22083707
Embry, A. E., Meng, X, Cantwell, A.M., Dube, P.H.,* and Yan Xiang.,* 2011. Enhancement of Immune Response to an Antigen Delivered by Vaccinia Virus by Displaying the Antigen on the Surface of Intracellular Mature Virion. Vaccine Jul 26;29(33):5331-9* corresponding authors PMID: 21664218
Cantwell, A. M., Bubeck, S., and Dube, P.H., 2010. YopH inhibits early pro-inflammatory cytokine responses during plague pneumonia. BMC Immunology. 11:29 PMID: 20565713
- Sabbah, A., Chang, T.H., Harnack, R., Frolich, V.C., Tominaga, K., Dube, P.H., Berton, M.T., Xiang, Y., and Bose, S. 2009. Activation of innate immune antiviral response by NOD2. Nat. Immunol. 10:1073-1080. PMID: 19701189
Bubeck, S. and Dube, P.H. 2007 CO92 D YopH is a potent live, attenuated plague vaccine. Clin. Vaccine Immunol. 14:1235-1238 PMID: 17652523
- Bubeck, S., Cantwell, A., and Dube, P.H., 2007. Delayed inflammatory response to primary pneumonic plague occurs both in out bred and inbred mice. Infect. Immun. 75:697-705. PMID: 17101642
AffiliationsAmerican Society For Microbiology
American Association of Immunologists
Editorial board member for Infection and Immunity
Frontiers in Cellular Microbiology
Lab Rooms: STRF - 279.1 C-H Phone: (210) 562-4175
- Angelene Cantwell, Senior Research Associate