Differential Chemokine Expression following Respiratory Virus Infection Reflects Th1- or Th2-Biased Immunopathology

Abstract

Respiratory syncytial virus (RSV) is a major viral pathogen of infants that also reinfects adults. During RSV infection, inflammatory host cell recruitment to the lung plays a central role in determining disease outcome. Chemokines mediate cell recruitment to sites of inflammation and are influenced by, and influence, the production of cytokines. We therefore compared chemokine production in a mouse model of immunopathogenic RSV infection in which either Th1 or Th2 immunopathology is induced by prior sensitization to individual RSV proteins. Chemokine expression profiles were profoundly affected by the nature of the pulmonary immunopathology: "Th2" immunopathology in BALB/c mice was associated with increased and prolonged expression of CCL2 (MCP-1), CXCL10 (IP-10), and CCL11 (eotaxin) starting within 24 h of challenge. C57BL/6 mice with "Th2" pathology (enabled by a deficiency of CD8 ؉ cells) also showed increased CCL2 production. No differences in chemokine receptor expression were detected. Chemokine blockers may therefore be of use for children with bronchiolitis.

Overcoming T-Cell-Mediated Immunopathology to Achieve Safe Respiratory Syncytial Virus Vaccination

“…In addition, studies performed on vacvG-immunized mice undergoing a challenge RSV infection suggest that the development of pulmonary eosinophilia is dependent upon CCL11 and CCL22 [44,48,49]. Taken together, these data suggest that the CCL17-and CCL22-dependent recruitment of Th2 cells and the CCL11-dependent recruitment of eosinophils contribute to pulmonary eosinophilia after RSV challenge of mice previously immunized with either vacvG or vacvF.…”

“…Th2 cells express the chemokine receptors CCR3 and CCR4 and are recruited into the lung by the production of the chemokines CCL11, CCL17, and CCL22 [47]. Eosinophils express CCR3 and CCR5 and are recruited into the lungs in part by CCL11 production after RSV challenge of vacvG-immunized mice [27,48,49]. In addition, RSV challenge of mice previously immunized with vacvG also results in a significant increase in the amount of CCL17 mRNA [50] and CCL22 protein [44] in the lung.…”

IL-13 Is Required for Eosinophil Entry into the Lung during Respiratory Syncytial Virus Vaccine-Enhanced Disease

“…In this context, our data suggest that the recruitment of Th2 cells by IL-13 is important for the downstream recruitment of eosinphils. CCL11 is known to be produced during RSV challenge of vvG-immunized mice (39), and depletion of CCL11 significantly decreases eosinophilia (49). We show that vvG-immunized IL-13-deficient mice undergoing challenge RSV infection have significantly decreased amounts of CCL11 protein in the lung as compared with wild-type mice (Fig.…”

Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG

“…Research efforts are needed to promote the design of safe, effective, and affordable vaccines capable of protecting against infection caused by RSV. This goal has turned out to be difficult, in part due to the virulence factors displayed by RSV, as well as the immunological component of the pathogenesis induced by this virus (38,39). Several independent studies have shown that RSV can modulate the host immune response in at least 2 different ways.…”