Heterogeneous pathological outcomes after experimental pH1N1 influenza infection in ferrets correlate with viral replication and host immune responses in the lung

Vidaña, Beatriz; Martínez, Jorge; Martínez-Orellana, Pamela; García Migura, Lourdes; Montoya, María; Martorell, Jaime; Majó, Natàlia

To determine the differences in viral signalling in the animals with different pathological outcomes, TLR3 gene expression was measured. TLR3 is an innate immune recognition receptor that has key roles in dsRNA detection, the initiation of innate immune responses, and the linking of innate and adaptive immunity to limit virus production [59] . It is known that aberrant TLR3 signalling plays a key role in mediating lung pathology and contributes to detrimental host inflammatory responses through the induction of proinflammatory molecules and the recruitment of CD8+ and phagocytic cells during IAV virus infection [42, 47, [59] [60] [61] . Polymorphisms that alter the function of TLR3 have been shown to be related to severe cases of pH1N1 and H5N1 influenza infection [20, 60, 62] . In the present work, the animals that developed severe lung lesions exhibited elevated TLR3 gene expression in the lungs that correlated with increased viral quantifications and increased recruitment of CD8+ and Lys + cells in these animals. However, the severely ill animals exhibited significantly lower expressions of IFNα, which is up-regulated by TLR3 induction. Nevertheless, this striking phenomenon may be indicative of inappropriate functioning of either the TLR3 or the Interferon receptor (IFNR)1 or impairments of the TLR3-IFNR1 pathway.