Abstract
Lung immunopathology is the major cause of influenza induced morbidity and mortality. DAP12 (DNAX-Activating Protein of 12kDa) is a membrane adaptor protein associated with varied surface receptors, and it is known to regulate influenza induced lung immunopathology. DAP12 associated receptor expression and their association with phenotype of bronchoalveolar lavage fluid (BAL) cells during swine influenza virus (SIV) infection in pigs is unknown. Since pig is a suitable large animal model for influenza research, our aim was to understand the effects of zoonotic SIV H1N1 infection on expression of DAP12 associated MDL-1, TREM-1 and TREM-2 receptors in pig BAL cells through qRT-PCR profiling. Results indicated that DAP12, MDL-1 and TREM-1 were constitutively expressed, but TREM-2 was upregulated. Stimulation of uninfected pig BAL cells in vitro using the cytokines IFNgamma and IL4 revealed that upregulation of TREM-2 was associated with enhanced expression of ARG1, but not with high levels of expression of TNFalpha and iNOS. ARG1 is a phenotype of alternatively activated alveolar macrophages that are known to protect lung tissue; hence TREM2 upregulation in pig BAL cells with similar phenotype suggests the possible beneficial role of these molecules in preventing the lung immunopathology. In conclusion, DAP12 and associated receptors are differentially expressed in pig BAL cells and TREM2 appears to have a beneficial role in regulating the lung immunopathology in SIV infection.
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