Dr. Bernard Arulanandam
The identification of novel therapeutic/prophylactic vaccine strategies and combinatorial antimicrobial therapies are of continued interest in the field of public health. Despite a better understanding of systemic immune mechanisms, there are still challenges facing the vaccine field particularly in the area of mucosal defenses. Mucosal surfaces form the major interface between the host and the environment, and constitute the first line of defense against pathogens. The mammalian mucosal immune system has evolved into an intricate network of tissues, lymphoid and mucus membrane-associated cells and effector mechanisms for host protection. The mucosal surface area in humans is estimated to be 300-400 square meters and represents a significant portal of entry for pathogens. Thus, there is an important need to understand the basic mechanisms of immune defenses at these specialized sites.
Immunopathogenesis of Chlamydia trachomatis
There currently is no licensed vaccine against Chlamydia trachomatis, the leading cause of sexually transmitted bacterial disease worldwide. Untreated chlamydial infections induce immunopathology in the uterus and fallopian tubes, causing pelvic inflammatory disease (PID) and complications such as ectopic pregnancy and infertility. Persistence is thought to be a major cause of chlamydia-induced diseases in humans and may be due to chlamydial ability to evade host immune responses. We are currently investigating various aspects of Chlamydia-induced pathogenesis utilizing genital and lung bacterial challenge models. The pathology produced by both genital (e.g., PID) and pulmonary infection of newborns (asthma-like consequences such as airway hyper-reactivity) result as a consequence of immunological sequeale to the primary or repeated infections with this pathogen. Overall, these studies provide valuable immunoregulatory insight into the design of viable vaccines against sexually transmitted disease resulting in infertility in adults and serious respiratory consequences in children born to infected mothers.
Respiratory Defenses against Pulmonary Tularemia
Francisella tularensis is an intracellular Gram-negative bacterium that is the causative agent of tularemia. Inhalation of F. tularensis results in severe disease and a high fatality rate in humans. There is limited information on localized respiratory defenses against this organism. Our laboratory has recently shown the involvement of mast cells in early defenses against pulmonary tularemia. We are currently examining the mechanisms by which mast cells modulate innate immune defenses against this pathogen, and as a model for other Gram negative bacteria. Moreover, we are characterizing the use of defined F. tularensis mutants as live attenuated vaccine candidates against pneumonic tularemia.
Mucosal Defenses Against Acinetobacter baumannii
Acinetobacter baumannii has emerged as an important nosocomial pathogen observed in injured military service personnel from the Middle East. Many multi-drug resistant strains of A. baumannii have been indentified which create additional therapeutic challenges for effective management of this infection. There is evidence to suggest that gastrointestinal colonization of A. baumannii in humans precedes the onset of other clinical conditions such as septicemia, pneumonia and wound sepsis, with little known about the interaction of this pathogen with the gastrointestinal (GI) tract. We have developed an oral-gastrointestinal (GI) challenge model with A. baumannii to examine the contribution of mucosal immune defenses against gastrointestinal colonization by this pathogen and the subsequent systemic manifestation of this infection.
Lab website: http://stceid.utsa.edu/arul/
Yu, J.J., Goluguri, T.R., Guentzel, M.N., Fosrthuber, T.G., Chambers, J.P., Murthy, A.K., Klose, K. E., Arulanandam B.P. Francisella tularensis T cell antigen identification using humanized HLA-DR4 transgenic mice. Clinical & Vacc. Immuno. 17 :215-222, 2010.
Chaganty, B.K.R., Murthy, A.K., Evani, S.J., Li., W., Guentzel, M.N., Chambers, J.P., Zhong, G., Arulanandam, B.P. Heat denatured enzymatically inactive recombinant chlamydial protease-like activity factor induces robust protective immunity against genital chlamydial challenge. Vaccine 28 :2323-2329. 2010.
Jupelli, M., Selby, D.M., Guentzel, M.N., Chambers, J.P., Forsthuber, T.G., Zhong, G., Murthy, A.K., Arulanandam, B.P., The contribution of IL-12/IFN- axis in protection against neonatal pulmonary Chlamydia muridarum challenge. J. Interferon & Cytokine Res. 30 :407-415. 2010. (Article was featured as cover art in 30:11, 2010)
Ray, H.J., Chu, P., Wu, T.H., Lyons, C.R., Guentzel, M.N., Klose, K.E., Arulanandam, B.P. The Fischer 344 rat reflects human susceptibility to Francisella pulmonary challenge and provides a new platform for virulence and protection studies. PLos One 5(4) e9952, 2010.
Li, W., Murthy, A.K., Guentzel, M.N., Chambers, J.P., Forsthuber, T.G., Seshu, J., Zhong, G., Arulanandam, B.P. Immunization with a combination of integral chlamydial antigens and a defined secreted protein induces robust immunity against genital chlamydial challenge. Infect. Immun. 78 :3942-3949 2010.
Rodriguez, A.R., Yu, J.-J., Murthy, A.K., Guentzel, M.N., Klose, K.E., Forsthuber, T.G., Chambers, J.P., Berton, M.T., Arulanandam, B.P. Mast cell/IL-4 control of Francisella tularensis replication and host cell death is associated with increased ATP production and phagosomal acidification. Mucosal Immunology 4 :217-226. 2011.
Evani, S.K., Murthy, A.K., Mareedu, N., Montgomery, R.K., Arulanandam B.P., Ramasubramaniam, A.K., Hydrodynamic regulation of monocyte inflammatory response to an intracellular pathogen. PLos One 6(1)e14492, 2011.
Murphey, C., Chang, S.Y., Arulanandam, B.P., Forsthuber, T.G. Induction of polyclonal CD8+ T cell activation and effector function by Pertussis toxin. Cellular Immuno. 267 :50-55. 2011.
Ji, N., Rao, N., Guentzel, M.N., Arulanandam, B.P., Forsthuber, T.G. Anaphylaxis and mortality induced by treatment of mice with anti-VLA-4 antibody and pertussis toxin. J. Immunol. 186 :2750-2756. 2011.
Nallaparaju, K., Yu, J.-J., Rodriguez, S.A., Zogaj, X., Guentzel, M.N., Seshu, J., Murthy, A.K., Chambers, J.P., Klose K.E., Arulanandam, B.P. Evasion of IFN- signaling by Francisella tularensis subsp. novicida is dependent upon Francisella Outer Membrane Protein C and mediated by acid phosphatase. PLos One. 6(3) e18201. 2011.
Thathaiah, P., Sanapala, S., Rodriguez, A.R., Yu, J-J., Murthy, A.K., Guentzel, M.N., Chambers, J.P., Arulanandam, B.P. Non FcR-bearing mast cells secrete sufficient IL-4 to control Francisella tularensis replication within macrophages. Cytokine, 55 :211-210. 2011.
Murthy, A.K., Chaganty, B.K.R., Troutman, T., Guentzel, M.N., Yu, J.-J., Ali, S.K., Chambers, J.P., Klose, K.E., Arulanandam, B.P. Mannose-containing carbohydrate side chains of non-specific human secretory IgA mediate inhibition of Vibrio cholerae biofilm formation. PLos One. 6(2) e16847. 2011.
Jupelli, M., Murthy, A.K., Chaganty, B.K.R., Selby, D.M., Vasquez, M.M., Mustafa, S.B., Henson, B.M., Seidner, S.R., Zhong, G., Guentzel, M.N., Arulanandam, B.P., Neonatal chlamydial pneumonia induces altered respiratory structure and function lasting into adult life. Lab. Invest. Epub. 2011.
Murthy, A.K., Li, W., Guentzel, M.N., Zhong, G., Arulanandam, B.P. Vaccination with a defined chlamydial secreted protein induces robust protection against female infertility following repeated genital chlamydial challenges. Vaccine 29 :2519-2522. 2011.
King, M.D., Guentzel, M.N., Arulanandam, B.P., Bodour, A.A., Brahmakshatriya, V., Lupiani, B., Chambers, J.P. Effects of bacterial secretions of the lower digestive tract of free-range waterfowl on influenza virus activation. J. Env. Micro. 77 :4119-4125, 2011.
Chu, P., Rodriguez, A., Arulanandam, B.P., Klose, K.E. Tryptophan prototrophy contributes to Francisella tularensis evasion of IFN--mediated host defense. Infect. Immun. 79 : 2356-2361, 2011.
Murthy, A.K., Li, W., Chaganty, B.K.R., Guentzel, M.N., Sesu, J., Forsthuber, T.G., Zhong, G., Arulanandam, B.P. TNF- production from CD8+ T cells mediates oviduct pathological sequelae following primary genital Chlamydia muridarum infection. Infect. Immun. 79 :2928-2935. 2011.
Chambers, J.P., Yu, J-J., Jupelli, M., Lopez-Ribot, J., Valdes, J.J., Arulanandam, B.P. Alpha-1 antitrypsin is markedly decreased following pulmonary F. tularensis challenge. Frontiers in Cellular and Infection Microbiology. 1(20):2011.
Li, W., Murthy, A.K., Chaganty, B.K.R., Guentzel, M.N., Seshu, J., Chambers, J.P., Zhong, G., Arulanandam, B.P. Immunization with denditic cells pulsed ex vivo with recombinant chlmaydial protease-like activity factor induces protective immunity against Chlamydia muridarum challenge. Frontiers in Microbial Immunology. 2(73): 2011.