title: Limited anti-inflammatory role for interleukin-1 receptor like 1 (ST2) in the host response to murine postinfluenza pneumococcal pneumonia.
abstract: Interleukin-1 receptor like 1 (ST2) is a negative regulator of Toll-like receptor (TLR) signaling. TLRs are important for host defense during respiratory tract infections by both influenza and Streptococcus (S.) pneumoniae. Enhanced susceptibility to pneumococcal pneumonia is an important complication following influenza virus infection. We here sought to determine the role of ST2 in primary influenza A infection and secondary pneumococcal pneumonia. ST2 knockout (st2(-/-)) and wild-type (WT) mice were intranasally infected with influenza A virus; in some experiments mice were infected 2 weeks later with S. pneumoniae. Both mouse strains cleared the virus similarly during the first 14 days of influenza infection and had recovered their weights equally at day 14. Overall st2(-/-) mice tended to have a stronger pulmonary inflammatory response upon infection with influenza; especially 14 days after infection modest but statistically significant elevations were seen in lung IL-6, IL-1β, KC, IL-10, and IL-33 concentrations and myeloperoxidase levels, indicative of enhanced neutrophil activity. Interestingly, bacterial lung loads were higher in st2(-/-) mice during the later stages of secondary pneumococcal pneumonia, which was associated with relatively increased lung IFN-γ levels. ST2 deficiency did not impact on gross lung pathology in either influenza or secondary S. pneumoniae pneumonia. These data show that ST2 plays a limited anti-inflammatory role during both primary influenza and postinfluenza pneumococcal pneumonia.
authors.affiliation: Center of Experimental and Molecular Medicine, Center of Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. d.c.blok@amc.uva.nl
authors.forename: Dana C
authors.initials: DC
authors.lastname: Blok
authors.forename: Koenraad F
authors.initials: KF
authors.lastname: van der Sluijs
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Onno J
authors.initials: OJ
authors.lastname: de Boer
authors.forename: Cornelis
authors.initials: C
authors.lastname: van 't Veer
authors.forename: Alex F
authors.initials: AF
authors.lastname: de Vos
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D006652:Histological Techniques; D007249:Inflammation / Q000209:etiology / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000150:complications* / Q000276:immunology; D011018:Pneumonia, Pneumococcal / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology*; D018709:Statistics, Nonparametric
chemical_list: C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D018123:Receptors, Interleukin