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J Cyst Fibros. 2018 Dec 7. pii: S1569-1993(18)30864-6. doi: 10.1016/j.jcf.2018.11.015. [Epub ahead of print]

Depletion of BAFF cytokine exacerbates infection in Pseudomonas aeruginosa infected mice.

Author information

1
Department of Human Genetics, McGill University, Montreal, Quebec, Canada; Program in Infectious Diseases and Immunity in Global Health, McGill University Health Center, Montreal, Quebec, Canada.
2
Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada; Program in Infectious Diseases and Immunity in Global Health, McGill University Health Center, Montreal, Quebec, Canada.
3
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
4
Department of Human Genetics, McGill University, Montreal, Quebec, Canada; Program in Infectious Diseases and Immunity in Global Health, McGill University Health Center, Montreal, Quebec, Canada. Electronic address: danuta.radzioch@mcgill.ca.

Abstract

BACKGROUND:

Cystic fibrosis (CF) is a genetic disease characterized by chronic inflammation of the lungs that is ineffective at clearing pathogens. B-cell activating factor (BAFF), a cytokine involved in the development of B-cells, is known to be elevated in CF patients with subclinical infections. We postulate that the elevated BAFF levels in CF patients might be triggered by Pseudomonas aeruginosa infection and it might play a protective role in the regulation of lung responses to infection.

METHODS:

To address this hypothesis, we used a well characterized model of CFTR.KO mice infected with a clinical strain of P. aeruginosa (PA508). We quantified cell types with flow cytometry, concentration of cytokines by ELISA tests, bacterial load by colony counting and lung physiology by metacholine-induced lung resistance.

RESULTS:

Our data demonstrates that BAFF is not elevated in uninfected CF mice, and infection with Pseudomonas leads to significant induction of this regulatory cytokine. We also demonstrate that the maintenance of BAFF levels and its induction during the infection is important for clearance of Pseudomonas infection as its depletion during the course of infection leads to decrease in the resolution of infection both in WT and CFTR-KO mice. Interestingly, the depletion of BAFF not only results in a depletion of B cells numbers but also to a significant decrease in the number of regulatory T cells in the non-infected lungs.

CONCLUSIONS:

Overall, our data demonstrate for the first time that BAFF is an important regulatory molecule helping to maintain the immunological response to infection and clearance of lung infection.

PMID:
30527891
DOI:
10.1016/j.jcf.2018.11.015

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