Transgenic mouse models support a protective role of type I IFN response in SARS-CoV-2 infection-related lung immunopathology and neuroinvasion

Autor: Nishant Ranjan Chauhan, Soumya Kundu, Ramyasingh Bal, Diya Chattopadhyay, Rinku Sahu, Subhash Mehto, Rina Yadav, Sivaram Krishna, Kautilya Kumar Jena, Sameekshya Satapathy, Anusha Pv, Krushna C. Murmu, Bharati Singh, Srinivas Patnaik, Sarita Jena, Krishnan H. Harshan, Gulam Hussain Syed, Mohammed M. Idris, Punit Prasad, Santosh Chauhan
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Reports, Vol 42, Iss 11, Pp 113275- (2023)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2023.113275
Popis: Summary: Type I interferon (IFN-I) response is the first line of host defense against invading viruses. In the absence of definite mouse models, the role of IFN-I in SARS-CoV-2 infection remains perplexing. Here, we develop two mouse models, one with constitutively high IFN-I response (hACE2; Irgm1−/−) and the other with dampened IFN-I response (hACE2; Ifnar1−/−), to comprehend the role of IFN-I response. We report that hACE2; Irgm1−/− mice are resistant to lethal SARS-CoV-2 infection. In contrast, a severe SARS-CoV-2 infection along with immune cell infiltration, cytokine storm, and enhanced pathology is observed in the lungs and brain of hACE2; Ifnar1−/− mice. The hACE2; Irgm1−/−Ifnar1−/− double-knockout mice display loss of the protective phenotype observed in hACE2; Irgm1−/− mice, suggesting that heightened IFN-I response accounts for the observed immunity. Taking the results together, we demonstrate that IFN-I protects from lethal SARS-CoV-2 infection, and Irgm1 (IRGM) could be an excellent therapeutic target against SARS-CoV-2.
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