Dr. Arulanandam’s research involves elucidating host-microbial interactions and cellular and molecular mechanisms involved in the induction of immune responses against infectious diseases. 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.