A critical role of IL-17 in modulating the B-cell response during H5N1 influenza virus infection

Abstract

Interleukin-17 (IL-17), a member of the IL-17 cytokine family, plays a crucial role in mediating the immune response against extracellular bacteria and fungi in the lung. Although there is increasing evidence that IL-17 is involved in protective immunity against H1 and H3 influenza virus infections, little is known about the role of IL-17 in the highly pathogenic H5N1 influenza virus infection. In this study, we show that H5N1-infected IL-17 knockout (KO) mice exhibit markedly increased weight loss, more pronounced lung immunopathology and significantly reduced survival rates as compared with infected wild-type controls. Moreover, the frequency of B cells in the lung were substantially decreased in IL-17 KO mice after virus infection, which correlated with reduced CXCR5 expression in B cells and decreased CXCL13 production in the lung tissue of IL-17 KO mice. Consistent with this observation, B cells from IL-17 KO mice exhibited a significant reduction in chemokine-mediated migration in culture. Taken together, these findings demonstrate a critical role for IL-17 in mediating the recruitment of B cells to the site of pulmonary influenza virus infection in mice.

Evaluation of the Sublingual Route for Administration of Influenza H5N1 Virosomes in Combination with the Bacterial Second Messenger c-di-GMP

“…In one study, IL-17RA knockout mice had improved survival following lethal influenza viral challenge as compared to wild type mice [60], suggesting a detrimental effect of IL-17 in the course of influenza infection. In contrast, another study showed that adoptively transferred Th17 effector cells can protect naïve mice against lethal influenza viral challenge [61] and it was recently shown in a mouse model that IL-17 plays a crucial role for B cell responses to influenza H5N1 infection [62]. We have previously found that IM vaccinated mice were protected against homologous HPAI challenge despite not producing IL-17 upon ex vivo re-stimulation of splenocytes [37], which suggests that IL-17 is dispensable in terms of effective vaccination against influenza.…”

A tale of two cytokines: IL-17 and IL-22 in asthma and infection

“…These data show that IL-17 is required for acute lung injury during influenza A infection. However, others have shown that IL-17 deletion of neutralization resulted in worsened influenza-induced weight loss and mortality [180,181]. In humans, rhinovirus synergizes with IL-17 to enhance IL-8 production by epithelial cells, which may help to promote the recruitment of immune cells to the airway [182].…”

The interaction of influenza H5N1 viral hemagglutinin with sialic acid receptors leads to the activation of human γδ T cells

“…7,8 HA is essential for triggering the host immune response to viral influenza infection for the production of neutralizing antibodies. 9,11 Therefore, understanding the immunogenicity of the H5N1 viral HA proteins is highly important for the development of immune therapeutics against influenza H5N1 viral infection.…”