Chlorine gas exposure increases susceptibility to invasive lung fungal infection.

Abstract

Chlorine (Cl₂) is a highly irritating and reactive gas with potential occupational and environmental hazards. Acute exposure to Cl₂ induces severe epithelial damage, airway hyperreactivity, impaired alveolar fluid clearance, and pulmonary edema in the presence of heightened inflammation and significant neutrophil accumulation in the lungs. Herein, we investigated whether Cl₂ exposure affected the lung antimicrobial immune response leading to increased susceptibility to opportunistic infections. Mice exposed to Cl₂ and challenged intratracheally 24 h thereafter with the opportunistic mold Aspergillus fumigatus demonstrated an >500-fold increase in A. fumigatus lung burden 72 h postchallenge compared with A. fumigatus mice exposed to room air. Cl₂-exposed A. fumigatus challenged mice also demonstrated significantly higher lung resistance following methacholine challenge and increased levels of plasma proteins (albumin and IgG) in the bronchoalveolar lavage fluid. Despite enhanced recruitment of inflammatory cells to the lungs of Cl₂-exposed A. fumigatus challenged mice, these cells (>60% of which were neutrophils) demonstrated a profound impairment in generating superoxide. Significantly higher A. fumigatus burden in the lungs of Cl₂ exposed mice correlated with enhanced production of IL-6, TNF-α, CXCL1, CCL2, and CCL3. Surprisingly, however, Cl₂-exposed A. fumigatus challenged mice had a specific impairment in the production of IL-17A and IL-22 in the lungs compared with mice exposed to room air and challenged with A. fumigatus. In summary, our results indicate that Cl₂ exposure markedly impairs the antimicrobial activity and inflammatory reactivity of myeloid cells in the lung leading to increased susceptibility to opportunistic pathogens.

• Authors: Melissa A Gessner, Stephen F Doran, Zhihong Yu, Chad W Dunaway, Sadis Matalon, Chad Steele
• Journal: American journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 304 Issue 11 Pg. L765-73 (Jun 01 2013) ISSN: 1522-1504 [Electronic] United States
• PMID: 23564508 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Chemokines
• Cytokines
• Interleukin-17
• Interleukin-6
• Interleukins
• Superoxides
• Chlorine
• interleukin-22

Topics

• Animals
• Aspergillosis (etiology)
• Bronchoalveolar Lavage Fluid (immunology)
• Chemokines (metabolism)
• Chlorine (toxicity)
• Cytokines (metabolism)
• Disease Susceptibility
• Interleukin-17 (biosynthesis)
• Interleukin-6 (biosynthesis)
• Interleukins (biosynthesis)
• Lung (immunology, microbiology, physiology)
• Lung Diseases, Fungal (etiology, immunology, microbiology)
• Male
• Mice
• Superoxides (metabolism)