Chancroid is a bacterial genital ulcer disease endemic to sub-Saharan Africa and Eastern Asia. The immune response to Haemophilus ducreyi, the etiologic agent of chancroid, is not very effective at either clearing organisms from an infected individual or at preventing subsequent H. ducreyi re-infections. The three specific aims described herein are designed to utilize and extend the swine model of chancroid to test hypotheses that relate to the mechanisms underlying this poor immune response.
Aim 1 assesses the host response to H. ducreyi by testing the hypothesis that H. ducreyi elicit predominantly cellular immunity, which is ineffective at clearing the infecting bacteria. The cytokine expression pattern of H. ducreyi specific CD4 and CD8 lymphocytes isolated from infected lesions will be examined.
In Aim 2 the bacterial contribution to inhibiting the immune response will be addressed by testing the hypothesis that the H. ducreyi CDT and hemolysin toxins block immunity development through their cytotoxic effect on immune effector cells.
This aim will be accomplished by comparing the kinetics and strength of immune development following inoculation with cdt/hem double mutants and wild type H. ducreyi, while also assessing differences in T cell cytokine expression and antigen specificity effected by mutant as compared to wild type organisms. The specific contribution of the toxins on the immune response will be examined by testing their effect on the development of antibody and cytotoxic T cells to hen egg lysozyme.
Aim 2 addresses the hypothesis that a vigorous bactericidal antibody response to H. ducreyi would result in more efficient clearing of organisms from infected tissue and prevent subsequent H. ducreyi re infection. An H. ducreyi outer membrane protein that is a target for bactericidal antibody has been identified. This protein will be tested for the ability to elicit a protective immune response to H. ducreyi.
|Godiwala, Nihal T; Vandewalle, Alain; Ward, Honorine D et al. (2006) Quantification of in vitro and in vivo Cryptosporidium parvum infection by using real-time PCR. Appl Environ Microbiol 72:4484-8|