Tissue-localized immune responses in people with cystic fibrosis and respiratory nontuberculous mycobacteria infection

Don Hayes, Jr.; Rajni Kant Shukla; Yizi Cheng; Emrah Gecili; Marlena R. Merling; Rhonda D. Szczesniak; Assem G Ziady; Jason C. Woods; Luanne Hall-Stoodley; Namal P.M. Liyanage; Richard T. Robinson

doi:10.1172/jci.insight.157865

Tissue-localized immune responses in people with cystic fibrosis and respiratory nontuberculous mycobacteria infection

Don Hayes, Jr.,¹ Rajni Kant Shukla,² Yizi Cheng,¹ Emrah Gecili,¹ Marlena R. Merling,² Rhonda D. Szczesniak,¹ Assem G Ziady,¹ Jason C. Woods,¹ Luanne Hall-Stoodley,² Namal P.M. Liyanage,² and Richard T. Robinson²

Published May 10, 2022 - More info

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Abstract

Nontuberculous mycobacteria (NTM) are an increasingly common cause of respiratory infection in people with cystic fibrosis (PwCF). Relative to those with no history of NTM infection (CF-NTM^NEG), PwCF and a history of NTM infection (CF-NTM^POS) are more likely to develop severe lung disease and experience complications over the course of treatment. In other mycobacterial infections (e.g. tuberculosis), an overexuberant immune response causes pathology and compromises organ function; however, since the immune profiles of CF-NTM^POS and CF-NTM^NEG airways are largely unexplored, it is unknown which if any immune responses distinguish these cohorts or concentrate in damaged tissues. Here we evaluated lung lobe-specific immune profiles of three cohorts (CF-NTM^POS, CF-NTM^NEG, and non-CF adults) and found that CF-NTM^POS airways are distinguished by a hyper-inflammatory cytokine profile. Importantly, the CF-NTM^POS airway immune profile was dominated by B cells, classical macrophages and the cytokines which support their accumulation. These and other immunological differences between cohorts, including the near absence of NK cells and complement pathway members, were enriched in the most damaged lung lobes. The implications of these findings for our understanding of lung disease in PwCF are discussed, as are how they may inform the development of host-directed therapies to improve NTM disease treatment.

Tissue-localized immune responses in people with cystic fibrosis and respiratory nontuberculous mycobacteria infection

Don Hayes, Jr.,¹ Rajni Kant Shukla,² Yizi Cheng,¹ Emrah Gecili,¹ Marlena R. Merling,² Rhonda D. Szczesniak,¹ Assem G Ziady,¹ Jason C. Woods,¹ Luanne Hall-Stoodley,² Namal P.M. Liyanage,² and Richard T. Robinson²

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Tissue-localized immune responses in people with cystic fibrosis and respiratory nontuberculous mycobacteria infection

Don Hayes, Jr.,1 Rajni Kant Shukla,2 Yizi Cheng,1 Emrah Gecili,1 Marlena R. Merling,2 Rhonda D. Szczesniak,1 Assem G Ziady,1 Jason C. Woods,1 Luanne Hall-Stoodley,2 Namal P.M. Liyanage,2 and Richard T. Robinson2

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Don Hayes, Jr.,¹ Rajni Kant Shukla,² Yizi Cheng,¹ Emrah Gecili,¹ Marlena R. Merling,² Rhonda D. Szczesniak,¹ Assem G Ziady,¹ Jason C. Woods,¹ Luanne Hall-Stoodley,² Namal P.M. Liyanage,² and Richard T. Robinson²