Human lung fibroblasts present bacterial antigen to autologous lung T helper cells

Abstract

Lung fibroblasts are key structural cells that reside in the submucosa where they are in contact with large numbers of CD4+ T helper cells. During severe viral infection and chronic inflammation the submucosa is susceptible to bacterial invasion by lung microbiota such as Nontypeable Haemophilus influenzae (NTHi). Given their proximity in tissue, we hypothesised that human lung fibroblasts play an important role in modulating T helper cell responses to NTHi. We demonstrate that fibroblasts express the critical CD4+ T cell antigen-presentation molecule HLA-DR within the human lung, and that this expression can be recapitulated in vitro in response to interferon (IFN)?. Furthermore, we observed that cultured lung fibroblasts could internalize live NTHi. While unable to express CD80 and CD86 in response to stimulation, fibroblasts expressed the co-stimulatory molecules 4-1BBL, OX-40L and CD70, all of which are related to memory T cell activation and maintenance. CD4+ T cells isolated from the lung were predominantly (mean 97.5%) CD45RO+ memory cells. Finally, cultured fibroblasts activated IFN? and IL-17A cytokine production by autologous, NTHi-specific lung CD4+ T cells, and cytokine production was inhibited by a HLA-DR blocking antibody. These results indicate a novel role for human lung fibroblasts in contributing to responses against bacterial infection through activation of bacteria-specific CD4+ T cells.

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Identifiers

ORCID for C. Mirella Spalluto: orcid.org/0000-0001-7273-0844

ORCID for Karl J. Staples: orcid.org/0000-0003-3844-6457

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