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B lymphocytes regulate airway granulocytic inflammation and cytokine production in a murine model of fungal allergic asthma

Cellular & Molecular Immunology volume 12, pages 202–212 (2015)Cite this article

Abstract

Sensitization to fungi often leads to a severe form of asthma that is particularly difficult to manage clinically, resulting in increased morbidity and hospitalizations in these patients. Although B lymphocytes might exacerbate asthma symptoms through the production of IgE, these cells might also be important in the protective response against inhaled fungi. Through cytokine release and T-cell interactions, these lymphocytes might also influence the development and maintenance of airway wall fibrosis. JH−/− mice lack the JH gene for the heavy chain component of antibodies, which is critical for B-cell function and survival. These animals have facilitated the elucidation of the role of B lymphocytes in a number of immune responses; however, JH−/− mice have not been used to study fungal allergy. In this study, we examined the role of B lymphocytes using an Aspergillus fumigatus murine fungal aeroallergen model that mimics human airway disease that is triggered by environmental fungal exposure. We compared disease progression in sensitized wild-type BALB/c and JH−/− mice that were exposed to repeated fungal exposure and found no differences in airway hyperresponsiveness, overall pulmonary inflammation or collagen deposition around the large airways. However, the levels of the Th2-type cytokines IL-4 and IL-13 were significantly attenuated in the airways of JH−/− mice relative to the BALB/c controls. By contrast, levels of the inflammatory cytokines IL-17A and IL-6 were significantly elevated in the JH−/− animals, and there was significantly more robust airway eosinophilia and neutrophilia than in control animals. Taken together, these findings demonstrate that B lymphocytes help to regulate granulocytic responses to fungal exposure in the pulmonary compartment.

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Acknowledgements

The authors wish to thank Dr Pawel Borowicz (North Dakota State University) and the Advanced Imaging and Microscopy Laboratory for imaging support using the Zeiss Z1 AxioObserver inverted microscope (NSF MRI-R2 0959512). We also thank Jessica Ebert for critical reading of the manuscript. These studies were funded by grants from the NIH (1R15HL117254-01 to JMS and 1R15AI101968-01A1 to GPD).

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  1. Jane M Schuh: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of North Dakota State University or the granting agencies.

Authors and Affiliations

  1. Department of Veterinary and Microbiological Sciences, North Dakota State University, Fargo, ND, USA

    Sumit Ghosh, Scott A Hoselton, Scott V Asbach, Breanne N Steffan, Steve B Wanjara, Glenn P Dorsam & Jane M Schuh

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  1. Sumit Ghosh
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  2. Scott A Hoselton
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Correspondence to Sumit Ghosh.

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Ghosh, S., Hoselton, S., Asbach, S. et al. B lymphocytes regulate airway granulocytic inflammation and cytokine production in a murine model of fungal allergic asthma. Cell Mol Immunol 12, 202–212 (2015). https://doi.org/10.1038/cmi.2014.103

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