IL-9 Regulates Pathology during Primary and Memory Responses to Respiratory Syncytial Virus Infection

Abstract

IL-9 is a cytokine of great current interest associated with allergic/Th2 responses. High levels of IL-9 are present in bronchial secretions from infants with respiratory syncytial virus (RSV) bronchiolitis. To test its effects in RSV disease with a Th2 profile, BALB/c mice were vaccinated with recombinant vaccinia virus expressing the RSV G protein. On RSV challenge, immunized mice developed augmented disease characterized by enhanced pulmonary Th2 and local IL-9 production peaking on days 7–10 of RSV infection. Depletion with anti-IL-9 Ab at vaccination or RSV challenge enhanced viral clearance. Depletion only at challenge had no effect on disease severity, whereas depletion at immunization and challenge enhanced Th1 responses, inhibited virus-specific IgG1 production, and enhanced disease severity. By contrast, depletion of IL-9 at immunization boosted IgG2a and inhibited the Th2 response and disease during subsequent infection without a concomitant increase in type 1 cytokines. Adoptive transfer of secondary memory CD4 T cells from the spleens of IL-9-depleted mice into naive recipients replicated many of the effects of depletion, indicating that IL-9 acts via CD4 T cells. Therefore, IL-9 is a previously unknown but key modulator of antiviral immunity, regulating T and B cell responses and having potent and specific effects on viral lung disease.

Epicutaneous Sensitization with Protein Antigen Induces Th9 Cells

“…Our results are in agreement with previous reports that showed enhanced Th2 responses due to IL-9 in different model systems (Forbes et al, 2008;Dodd et al, 2009). The cellular sources of IL-9 include mast cells, natural killer T (NKT) cells, and T cells (Noelle and Nowak, 2010).…”

“…Forbes et al (2008) reported that intestinal IL-9 overexpression predisposed to oral antigen sensitization. Dodd et al (2009) demonstrated that depletion of IL-9 during the sensitization phase of syncytial virus infection suppressed a Th2 response. Arendse et al (2005) showed that IL-9 could influence the Th dichotomy in Leishmaniasis by promoting deleterious Th2 responses in BALB/c mice.…”

T helper 9 cells induced by plasmacytoid dendritic cells regulate interleukin-17 in multiple sclerosis

“…On the other hand, IL-9 is a cytokine implicated in human and murine asthma, anaphylaxis, resistance to nematode infection, antiviral immunity and tumorigenesis [60][61][62][63][64][65][66][67][68][69]. The role of IL-9 in autoimmunity has been investigated in the mouse model of MS, experimental autoimmune encephalomyelitis (EAE).…”

Local cytokine response upon respiratory syncytial virus infection

“…As cytokines have been shown to play an important role during RSV pathology, they could be considered as potential pharmacological targets for preventing disease in severe cases of infection or predictors for prognosis [125][126]. In fact, blockade of certain cytokine/chemokines could be used to reduce lung pathology caused by RSV.…”