Comparison of cytokine profiles induced by nonlethal and lethal doses of influenza A virus in mice
- Lucia Turianová
- Veronika Lachová
- Darina Svetlíkova
- Anna Kostrábová
- Tatiana Betáková
Affiliations: Biomedical Research Center‑Slovak Academy of Sciences, Institute of Virology, 84505 Bratislava, Slovak Republic, Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, 84215 Bratislava, Slovak Republic
- Published online on: October 14, 2019 https://doi.org/10.3892/etm.2019.8096
Copyright: © Turianová
et al. This is an open access article distributed under the
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Influenza viruses are among the most common human pathogens and are responsible for causing extensive seasonal morbidity and mortality. To investigate the immunological factors associated with severe influenza infection, the immune responses in mice infected with nonlethal (LD0) doses of A/PR/8/34 (H1N1) influenza virus were compared with those of mice infected with a lethal dose (LD100) of the virus. The virus titer and activation of retinoic acid‑inducible gene (RIG)‑I‑like receptor signaling pathways were similar in the mice infected with LD0 and LD100 at 2 days post‑infection; however, mice infected with LD100 exhibited a greater abundance of cytokines and a more diverse cytokine profile. Infection with LD100 induced the expression of the following factors: Interleukins (ILs), IL‑4, IL‑7, IL‑10, IL‑11, IL‑12p40, IL‑13 and IL‑15; inflammatory chemokines, C‑C motif chemokine ligand (CCL)2, CCL3/4, CCL12, CCL17, CCL19; and lung injury‑associated cytokines, leptin, leukaemia inhibitory factor, macrophage colony stimulating factor, pentraxin (PTX)2 and PTX3, WNT1‑inducible‑signaling pathway protein 1, matrix metallopeptidase (MMP)‑2, MMP‑3, proprotein convertase subtilisin/kexin type 9, and T cell immunoglobulin and mucin domain. Switching in macrophage polarization from M1 to M2 was evidenced by the increase in M2 markers, including arginase‑1 (Arg1) and early growth response protein 2 (Egr2), in the lungs of mice infected with LD100. Since IL‑12 and interferon‑γ are the major T helper (Th)1 cytokines, increased expression of interferon regulatory factor 4, IL‑4, IL‑10 and IL‑13 promoted the differentiation of naïve CD4+ T cells into Th2 cells. In conclusion, the present study identified key cytokines involved in the pathogenicity of influenza infection, and demonstrated that lethal influenza virus infection induces a mixed Th1/Th2 response.