- Title
- PD-L1 promotes early-life chlamydia respiratory infection-induced severe allergic airway disease
- Creator
- Starkey, Malcolm R.; Nguyen, Duc H.; Brown, Alexandra C.; Essilfie, Ama-Tawiah; Kim, Richard Y.; Yagita, Hideo; Horvat, Jay C.; Hansbro, Philip M.
- Relation
- American Journal of Respiratory Cell and Molecular Biology Vol. 154, Issue 4, p. 493-503
- Publisher Link
- http://dx.doi.org/10.1165/rcmb.2015-0204OC
- Publisher
- American Thoracic Society
- Resource Type
- journal article
- Date
- 2016
- Description
- However, the immune responses that protect against early-life infection and the mechanisms that lead to chronic lung disease are incompletely understood. In the current study we investigated the role of programmed death (PD)-1 and its ligands PD-L1 and PD-L2 in promoting early-life Chlamydia respiratory infection, and infection-induced airway hyperresponsiveness (AHR) and severe allergic airway disease (AAD) in later life. Infection increased PD-1 and PD-L1, but not PD-L2, mRNA expression in the lung. Flow cytometric analysis of whole lung homogenates identified monocytes, dendritic cells, CD4+ and CD8+ T cells as major sources of PD-1 and PD-L1. Inhibition of PD-1 and PD-L1, but not PD-L2, during infection ablated infection-induced AHR in later life. Given that PD-L1 was the most highly up-regulated and its targeting prevented infection-induced AHR, subsequent analyses focused on this ligand. Inhibition of PD-L1 had no effect on Chlamydia load, but suppressed infection-induced pulmonary inflammation. Infection decreased the levels of the IL-13 decoy receptor in the lung, which were restored to baseline levels by inhibition of PD-L1. Finally, inhibition of PD-L1 during infection prevented subsequent infection-induced severe allergic airways disease in later-life, by decreasing IL-13 levels, Gob-5 expression, mucus production and AHR. Thus, early-life Chlamydia respiratory infection-induced PD-L1 promotes severe inflammation during infection, permanent reductions in lung function and the development of more severe AAD in later life.
- Subject
- infant; chlamydia respiratory infection; PD-L1; airway hyperresponsiveness; asthma
- Identifier
- http://hdl.handle.net/1959.13/1310201
- Identifier
- uon:21997
- Identifier
- ISSN:1535-4989
- Language
- eng
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