Pneumocystis-Driven Inducible Bronchus-Associated Lymphoid Tissue Formation Requires Th2 and Th17 Immunity

Publication date: 28 March 2017
Source:Cell Reports, Volume 18, Issue 13
Author(s): Taylor Eddens, Waleed Elsegeiny, Maria de la Luz Garcia-Hernadez, Patricia Castillo, Giraldina Trevejo-Nunez, Katelin Serody, Brian T. Campfield, Shabaana A. Khader, Kong Chen, Javier Rangel-Moreno, Jay K. Kolls
Inducible bronchus-associated lymphoid tissue (iBALT) is an ectopic lymphoid structure composed of highly organized T cell and B cell zones that forms in the lung in response to infectious or inflammatory stimuli. Here, we develop a model for fungal-mediated iBALT formation, using infection with Pneumocystis that induces development of pulmonary lymphoid follicles. Pneumocystis-dependent iBALT structure formation and organization required CXCL13 signaling. Cxcl13 expression was regulated by interleukin (IL)-17 family members, as Il17ra^−/−, Il17rb^−/−, and Il17rc^−/− mice failed to develop iBALT. Interestingly, Il17rb^−/− mice have intact Th17 responses, but failed to generate an anti-Pneumocystis Th2 response. Given a role for Th2 and Th17 immunity in iBALT formation, we demonstrated that primary pulmonary fibroblasts synergistically upregulated Cxcl13 transcription following dual stimulation with IL-13 and IL-17A in a STAT3/GATA3-dependent manner. Together, these findings uncover a role for Th2/Th17 cells in regulating Cxcl13 expression and provide an experimental model for fungal-driven iBALT formation.

Graphical abstract

Teaser

Eddens et al. develop a model for fungal-inducible bronchus-associated lymphoid tissue (iBALT) formation driven by infection or exposure to Pneumocystis. Pneumocystis induces Th2 and Th17 immunity, both of which are required for iBALT formation.


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