Human rhinovirus induced cytokine/chemokine responses in human airway epithelial and immune cells.

Devi Rajan,Larry J Anderson,Hannah B Kopleman,F Eun-Hyung Lee,Xiaoyan Lu,Courtney E Mccracken,Shuya Y Kyu,Juliet Spencer

doi:10.1371/journal.pone.0114322

Devi Rajan, Larry J Anderson + Show 6 more

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https://doi.org/10.1371/journal.pone.0114322

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Abstract

Infections with human rhinovirus (HRV) are commonly associated with acute upper and lower respiratory tract disease and asthma exacerbations. The role that HRVs play in these diseases suggests it is important to understand host-specific or virus-specific factors that contribute to pathogenesis. Since species A HRVs are often associated with more serious HRV disease than species B HRVs, differences in immune responses they induce should inform disease pathogenesis. To identify species differences in induced responses, we evaluated 3 species A viruses, HRV 25, 31 and 36 and 3 species B viruses, HRV 4, 35 and 48 by exposing human PBMCs to HRV infected Calu-3 cells. To evaluate the potential effect of memory induced by previous HRV infection on study responses, we tested cord blood mononuclear cells that should be HRV naïve. There were HRV-associated increases (significant increase compared to mock-infected cells) for one or more HRVs for IP-10 and IL-15 that was unaffected by addition of PBMCs, for MIP-1α, MIP-1β, IFN-α, and HGF only with addition of PBMCs, and for ENA-78 only without addition of PBMCs. All three species B HRVs induced higher levels, compared to A HRVs, of MIP-1α and MIP-1β with PBMCs and ENA-78 without PBMCs. In contrast, addition of CBMCs had less effect and did not induce MIP-1α, MIP-1β, or IFN-α nor block ENA-78 production. Addition of CBMCs did, however, increase IP-10 levels for HRV 35 and HRV 36 infection. The presence of an effect with PBMCs and no effect with CBMCs for some responses suggest differences between the two types of cells possibly because of the presence of HRV memory responses in PBMCs and not CBMCs or limited response capacity for the immature CBMCs relative to PBMCs. Thus, our results indicate that different HRV strains can induce different patterns of cytokines and chemokines; some of these differences may be due to differences in memory responses induced by past HRV infections, and other differences related to virus factors that can inform disease pathogenesis.

Highlights

Human rhinovirus (HRV) is a positive, single stranded RNA virus which belongs to the genus Enterovirus in the family Picornaviridae
Since HRV 14 is a species B and HRV 16 a species A virus and both utilize ICAM-1 receptor, we hypothesized that some of the differences in cytokines and chemokines we noted might be associated with one or the other species. To look into this possibility, we investigated 3 other species A HRV 25, 31 and 36 and 3 other species B viruses HRV 4, 35 and 48 using the two-chamber tissue culture system. These HRVs are among the many detected in recent studies of acute respiratory disease, replicate in our tissue culture system, include HRVs using both receptors, and some, HRV 14, 16, and 48, have been previously described in studies of the HRV immune response [26, 27, 28, 29], In addition, we investigated the response of cord blood mononuclear cells (CBMCs) to HRV infection and compared these responses to those by adult peripheral blood mononuclear cells (PBMCs)
For example in some studies, species A and C HRVs have stronger associations with exacerbations of asthma and acute respiratory illness than species B HRVs [17, 18, 19, 20, 21, 22, 23, 24]. These epidemiologic observations and our recent finding [26] that HRV 14 and HRV 16 infection of calu-3 cells with PBMCs induce different cytokine and chemokine responses led us to look for strain and species differences in responses induced by in vitro HRV infection

Summary

Introduction

Human rhinovirus (HRV) is a positive, single stranded RNA virus which belongs to the genus Enterovirus in the family Picornaviridae. More than 100 genotypes of HRVs have been identified that are phylogenetically distinct and divisible into three species, A, B, and C. HRV infection of cells triggers cytokine and chemokine production that may contribute to disease [9, 10, 11, 12, 13, 14, 15, 16]. Since epidemiologic studies suggest that species B virus is less commonly and species A and C HRVs are more frequently associated with disease [17, 18, 19, 20, 21, 22, 23, 24], we wondered if species differences in disease may be accompanied by differences in induction of cytokines or chemokines

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