Picascia, Antonietta (2015) Pathogenic mechanisms of tissue damage mediated by Bartonella henselae in preclinical models and in patients with advanced heart failure awaiting transplantation. [Tesi di dottorato]

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Abstract

Heart transplantation outcome is related to effects of immunological and no immunological factors. The major immunological factors are the HLA, the autoimmunity and the inflammation, while the non-immunological factors include among other the hypertension, diabetes, immunosuppressive therapies, cancer and infections. Infectious complications represent a significant source of morbidity and mortality in heart transplantation recipients. However, few studies have been focused on the incidence and the types of infection in patients awaiting heart transplantation and the impact of pre-transplantation infections on the early post-transplantation period. Often these are opportunistic infections due to virus, bacteria and fungi that can be difficult to identify, to treat, and can be lethal in the immunosuppressed patients. Most post-transplantation infections represent reactivation of latent or quiescent infections that had been contracted prior to transplantation. Recently, several evidences have showed the incidence of B. henselae infections in solid organ transplantation recipients. B. henselae infections are responsible for a widening spectrum of human diseases, ranging from self-limited to life-threatening and show different course and organ involvement due to the balance between host and pathogen. The role of the host immune response to B. henselae is critical in preventing progression to systemic disease. Indeed, in immunocompromised patients, such as solid organ transplanted subjects, B. henselae infection results in severe disseminated disease and pathologic vasoproliferation with involvement of different organs mainly due to vasoproliferative lesions. Furthermore, B. henselae can persist in primary niche prior to blood-stage infection. In vitro and in vivo studies have demonstrated that endothelial progenitor cells are able to internalize B. henselae and they are eligibile as primary niche. Susceptibility to infections and many other human diseases arises through the complex interaction between environmental and host genetic factors including the HLA molecules. In our study, we have found a B. henselae significant antibody positivity rate of 21% in patients awaiting heart transplantation enrolled in our Regional Reference list for organ transplantation. We have demonstrated a significant correlation between the B. henselae infection and the presence of HLA-B*35 allele and a significant impairment of number of circulating endothelial progenitor cells in patients with advanced heart failure. In addition, we have also evaluated the tissue damage in a model of immunocompromised mice infected with B. henselae by revealing a strong deposition of collagen after B. henselae infection and an increase of endothelial progenitor cell number that can suggest an involvement of these cells in the immune response of mice infected but also in the triggering the vasoproliferative process. Our retrospective observational study, although performed on a small number of patients only in pre-transplantation time suggests that B. henselae, together with other emerging bacteria, should be included as a routine analysis in the list of opportunistic infections.

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