Rhinovirus-induced macrophage cytokine expression does not require endocytosis or replication

Thomas G. Saba, Yutein Chung, Jun Young Hong, Uma S. Sajjan, J. Kelley Bentley, Marc B. Hershenson

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


Rhinovirus (RV) is responsible for the majority of virus-induced asthma exacerbations. We showed previously that RV infection of ovalbumin-sensitized and -challenged BALB/c mice induces productionof type 2 cytokines fromM2-polarizedmacrophages. In the present study, we sought to determine the mechanism of RV-induced cytokine expression.We infected bonemarrow- derivedmacrophages (BMMs) fromBALB/c micewith RVserotype 1B, aminor group virus that infects mouse cells. Selected cultures were pretreated with IL-4, a type 2 cytokine increased in allergic asthma. RV infection of untreated cells increasedmessengerRNAand protein expression of the M1cytokinesTNF-a,CXCL1, and IL-6 but failed to induce expression of theM2 cytokines CCL22 and CCL24. Cells pretreated with IL-4 showed decreased expression ofM1 cytokines but increased expression of Ym-1, Arg-1 (M2 markers), CCL22, and CCL24. Infection with ultraviolet (UV)-irradiated, replication-deficient RV elicited similar cytokine responses, suggesting that the outcome is replication independent. Consistent with this, viral RNA copy number did not increase in RV-treated BMMs or bronchoalveolar macrophages. RVinduced cytokine expression was not affected when cells were pretreated with cytochalasin D, suggesting that viral endocytosis is not required for the response. Finally, RV-induced cytokine expression and viral attachment were abolished in BMMs from myeloid differentiation factor 88 and Toll-like receptor (TLR)2 KO mice, suggesting a specific requirement of TLR2.We conclude thatRVelicits a proinflammatory cytokine response in BMMs through a cellsurface-mediated, TLR2-dependentmechanism that does not require viral endocytosis or replication.

Original languageEnglish
Pages (from-to)974-984
Number of pages11
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Issue number5
Publication statusPublished - 2014 May

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology


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