Tissue-localized immune responses in people with cystic fibrosis and respiratory nontuberculous mycobacteria infection
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-NTMNEG), PwCF and a history of NTM infection (CF-NTMPOS) are more likely to develop severe lung disease and experi...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2022-06-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.157865 |
| _version_ | 1811329642596925440 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Don Hayes Jr. |
| collection | DOAJ |
| description | 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-NTMNEG), PwCF and a history of NTM infection (CF-NTMPOS) 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-NTMPOS and CF-NTMNEG 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 3 cohorts (CF-NTMPOS, CF-NTMNEG, and non-CF adults) and found that CF-NTMPOS airways are distinguished by a hyperinflammatory cytokine profile. Importantly, the CF-NTMPOS airway immune profile was dominated by B cells, classical macrophages, and the cytokines that 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. |
| first_indexed | 2024-04-13T15:47:24Z |
| format | Article |
| id | doaj.art-4eb2e4ec73f04f1db4ca8742c6cfb12c |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-04-13T15:47:24Z |
| publishDate | 2022-06-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-4eb2e4ec73f04f1db4ca8742c6cfb12c2022-12-22T02:40:56ZengAmerican Society for Clinical investigationJCI Insight2379-37082022-06-01712Tissue-localized immune responses in people with cystic fibrosis and respiratory nontuberculous mycobacteria infectionDon Hayes Jr.Rajni Kant ShuklaYizi ChengEmrah GeciliMarlena R. MerlingRhonda D. SzczesniakAssem G. ZiadyJason C. WoodsLuanne Hall-StoodleyNamal P.M. LiyanageRichard T. RobinsonNontuberculous 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-NTMNEG), PwCF and a history of NTM infection (CF-NTMPOS) 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-NTMPOS and CF-NTMNEG 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 3 cohorts (CF-NTMPOS, CF-NTMNEG, and non-CF adults) and found that CF-NTMPOS airways are distinguished by a hyperinflammatory cytokine profile. Importantly, the CF-NTMPOS airway immune profile was dominated by B cells, classical macrophages, and the cytokines that 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.https://doi.org/10.1172/jci.insight.157865Infectious diseasePulmonology |
| spellingShingle | 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 Tissue-localized immune responses in people with cystic fibrosis and respiratory nontuberculous mycobacteria infection JCI Insight Infectious disease Pulmonology |
| title | Tissue-localized immune responses in people with cystic fibrosis and respiratory nontuberculous mycobacteria infection |
| title_full | Tissue-localized immune responses in people with cystic fibrosis and respiratory nontuberculous mycobacteria infection |
| title_fullStr | Tissue-localized immune responses in people with cystic fibrosis and respiratory nontuberculous mycobacteria infection |
| title_full_unstemmed | Tissue-localized immune responses in people with cystic fibrosis and respiratory nontuberculous mycobacteria infection |
| title_short | Tissue-localized immune responses in people with cystic fibrosis and respiratory nontuberculous mycobacteria infection |
| title_sort | tissue localized immune responses in people with cystic fibrosis and respiratory nontuberculous mycobacteria infection |
| topic | Infectious disease Pulmonology |
| url | https://doi.org/10.1172/jci.insight.157865 |
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