Comparative immunopathology of Cetacean Morbillivirus infection in free-ranging dolphins from Western Mediterranean, Northeast-Central, and Southwestern Atlantic

Josué Diaz-Delgado, Katia R. Groch, Rodrigo Ressio, Isis P.J. Riskallah, Eva Sierra, Simona Sacchini, Oscar Quesada-Canales, Manuel Arbelo, Antonio Fernández, Elitiere Santos-Neto, Joana Ikeda, Rafael Ramos de Carvalho, Alexandre de Freitas Azevedo, José Lailson Brito Jr, Leonardo Flach, Cristina T. Kanamura, Natalia C.C.A. Fernandes, Bruno Cogliati, Cinzia Centelleghe, Sandro Mazzariol, Ludovica Di Renzo, Gabriella Di Francesco, Giovanni Di Guardio, José Luiz Catão-Dias

Cetacean morbillivirus (CeMV; Paramyxoviridae) causes fatalities in odontocetes and mysticetes worldwide; however, the pathogenesis of CeMV infection is not fully resolved. Therefore, this study was aimed at characterizing and comparing immunophenotypic profiles of local immune responses in lymphoid organs (lymph nodes, spleen), lung and CNS in CeMV-molecularly (RT-PCR)-positive cetaceans from Western Mediterranean, Northeast-Central and Southwestern Atlantic. Immunohistochemical (IHC) analyses targeted molecules of immunologic interest: caspase 3, CD3, CD20, CD57, CD68, FoxP3, MHCII, Iba1, IFN?, IgG, IL4, IL10, lysozyme, TGF? and PAX5. We detected consistent CeMV-associated inflammatory response patterns. Within CNS, inflammation was dominated by CD3+ (T cells), and CD20+ and PAX5+ (B cells) lymphocytes, accompanied by fewer Iba1+, CD68+ and lysozyme+ histiocytes, mainly in striped dolphins and bottlenose dolphins. Multicentric lymphoid depletion was characterized by reduced numbers of T cells and B cells, more pronounced in Guiana dolphins. Striped dolphins and bottlenose dolphins often had hyperplastic (regenerative) phenomena involving the aforementioned cell populations, particularly chronically infected animals. In the lung, there was mild to moderate increase in T cells, B cells and histiocytes. Additionally, there was a generalized increased expression of caspase 3 in lymphoid, lung and CNS tissues. Apoptosis, therefore, is believed to play a major role in generalized lymphoid depletion and likely overt immunosuppression during CeMV infection. No differences were detected regarding cytokine immunoreactivity in lymph nodes, spleen and lung from infected and non-infected dolphins by semiquantitative analysis; however, there was striking immunoreactivity for IFN? in the CNS of infected dolphins. These novel results set the basis for tissue-specific immunophenotypic responses during CeMV infection in three highly susceptible delphinid species. They also suggest a complex interplay between viral and host’s immune factors, thereby contributing to gain valuable insights into similarities and differences of CeMV infection’s immunopathogenesis in relation to body tissues, CeMV strains and cetacean hosts.

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