Patología experimental. Immunohistochemical characterization of apoptosis in lymphoid organs and the liver of naturally porcine circovirus type 2 (pcv2) infected pigs

Resumo

This thesis is focused on the involvement of apoptosis in the development of lymphocyte depletion and hepatitis lesions associated with postweaning multisystemic wasting syndrome (PMWS), a pig disease in which porcine circovirus type 2 (PCV2) is the essential infectious cause. PMWS is believed to be a "multifactorial" disease, and is clinically characterized by wasting and poor response to therapeutic treatments. Main pathological features are lymphoid depletion, lymphopenia, anaemia, hepatitis, nephritis, enteritis and pneumonic lesions. It is believed that PMWS affected pigs suffer from immunosuppression. Mechanisms underlying the pathogenesis of the disease still are poorly understood. Viruses often modulate the cell apoptotic machinery to succeed in host infection; these viral mechanisms may induce lymphocyte and hepatocyte death among other cell types. Apoptosis involvement in PMWS lesions development was suggested in the first pathologic descriptions of the disease based on morphological criteria. Further, apoptosis has been investigated to a certain degree in hepatitis and lymphoid lesion from PMWS affected pigs by the TUNEL technique. In the present thesis we evaluated apoptosis from PMWS cases by in situ detection of anti-active caspase-3 in hepatic and lymphoid lesions. Our results indicated that liver cell damage in PCV2 hepatitis is mediated by induction of apoptosis, but this does not seem to be the main mechanism involved in lymphoid depletion lesions. These results bring a new insight into the possible role of apoptosis involvement in PMWS. The potential effect of PCV2 ORF3 protein inducing apoptosis in vivo in pigs suffering from PMWS under conventional field circumstances seems feasible according to our results, at least in the liver. Our results also suggest that other mechanisms may be involved in the pathogenesis of lymphoid depletion, such as inhibited proliferation of thymocytes, supporting the hypothesis proposed by other studies. The ma