|SINKORA, MAREK - Academy Of Sciences Of The Czech Republic (ASCR)|
|BUTLER, JOHN - University Of Iowa|
|POTOCKOVA, HANA - Academy Of Sciences Of The Czech Republic (ASCR)|
|SINKOROVA, JANA - Academy Of Sciences Of The Czech Republic (ASCR)|
Submitted to: Veterinary Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/18/2014
Publication Date: 9/4/2014
Citation: Sinkora, M., Butler, J.E., Lager, K.M., Potockova, H., Sinkorova, J. 2014. The comparative profile of lymphoid cells and the T and B cell spectratype of germ-free piglets infected with viruses SIV, PRRSV or PCV2. Veterinary Research. 45:91.
Interpretive Summary: The leading causes of respiratory disease in young pigs are infections with swine influenza virus (SIV), porcine circovirus type 2 (PCV2), and porcine reproductive and respiratory syndrome virus (PRRSV). These viruses cause significant economic losses for the pork industry. Although it is not well understood, viral infections can subvert the immune system in man and animals through a variety of mechanisms. Vaccines are available for each of these viruses; however, they have variable efficacy which is dependent on many factors. Understanding how these viruses cause disease may lead to improved vaccines and reduced economic losses. Investigating the mechanisms in conventional pig models is confounded by natural exposure to different microbes, concurrent infections, and the variable effects of passively acquired maternal antibodies and regulatory factors. The isolator germ-free piglet model was used to measure the direct effect of SIV, PCV2 and PRRSV on the naive immune systems of neonatal piglets. As expected, the germ-free pigs cleared the SIV infection quickly, but they did not clear the PCV2 or PRRSV infections during the course of the experiments. The immune response against SIV was used as a "normal" standard to which the PCV2 and PRRSV immune responses were compared. Both immune responses were abnormal, but different in character indicating that each virus had a unique capacity to thwart the pig's immune system. This basic knowledge will be applied towards a better understanding of how each virus affects pigs which will help design targeted experiments to improve vaccines.
Technical Abstract: Parallel studies on the cellular aspects of the immune response of germ-free isolator piglets experimentally infected with SIV, PRRSV or PSV2 were compared with special emphasis on the response of alphabeta T, gammadelta T, B and NK cells. PRRSV infection caused an extraordinary local increase in lymphocytes and dysregulation of the B cell compartment which allows for the generation of high levels of antibody-forming B cells and plasma cells. This can explain the hypergammaglobulinemia and polyspecific antibodies that characterize this infection. Our findings also suggest that B cell dysregulation is characterized by omission or restriction of normal activation pathway and is dependent on T helper cells. Gammadelta T cells are also increased and may play a protective role in the immune response against PRRSV infection. PCV2 infection also caused dysregulation of immune response but by overproduction of highly activated MHC-II+ T cytotoxic cells, the restriction of the T helper compartment and by the generation of a high proportion of Treg cells. Thus, immunosuppression combined with T cytotoxic hyperactivity may be the cause of the lymphopenia that is a hallmark of PCV2 infection. While the frequency and subpopulation usage of B cell subpopulations appeared to be normal, PCV2 infection was characterized by exceptional high frequency of clonally unique IgA+ B cells, presumably selected at the site of infection. These findings may help to elucidate the mechanisms by which PRRSV and PCV2 modulate the host immune system and may provide clues for the design of new vaccines.