SCVD Faculty

Abdelhakim Ben Nasr, PhD

The long term research interests in the Laboratory involve the study of human immune responses and the development of a vaccine against the highly virulent bacteria Francisella tularensis (Ft). Specifically, current projects are focused on developing a mouse model to investigate the immune mechanisms necessary for establishing protective immunity against inhalation infection in mice, and the investigation of the interactions of Ft with two important modules of the human immune system: the complement system and dendritic cells (DCs).

Understanding the lung immune response and developing a vaccine that would protect against respiratory Ft infections is crucially important, given that any biological weapon using Francisella would use the aerosolization mechanism for dispersal. We recently described a mouse model, in which we have shown that mice infected via intra-nasal challenge with virulent Ft and then treated with levofloxacin developed protective immunity against subsequent intra-nasal challenge with the same virulent Ft strain. Furthermore, sera from these challenged and rescued mice were shown to be protective when passively transferred to normal, naive, mice. Thus, this model might provide valuable insight into a number of questions with regard to the rational design of a vaccine against inhalation infection with virulent Francisella.

The complement system is involved in the immune responses both as a sensor that recognizes infectious agents and as a generator of effector molecules that mediate inflammation and the clearance of bacterial pathogens. DCs, the professional antigen-presenting cells that are involved in bridging innate and adaptive immunity, are able to phagocytose Ft through complement receptors and are activated by this pathogen. F. tularensis is both serum/complement resistant and has an enormous ability to grow in the intracellular milieu of macrophages and DCs. Further, the complement system is an essential arm of the adaptive immune response, and dendritic cells have a pivotal role in activating the cellular arm of this immune response.

Studies of the molecular mechanisms of resistance to complement and phagocytosis-mediated killing should contribute to our understanding of the immune evasion strategies of this highly virulent pathogen and may lead to the generation of therapeutic and diagnostic tools to control tularemia.

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