Early Immunological Response to German Cockroach Frass Exposure Induces a Th2/Th17 Environment

• Published in: Journal of innate immunity Vol. 3; no. 2; pp. 167 - 179
• Main Authors: Page, Kristen, Zhou, Ping, Ledford, John R., Day, Scottie B., Lutfi, Riad, Dienger, Krista, Lewkowich, Ian P.
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.01.2011; S. Karger AG
• Subjects: Animals; Biological and medical sciences; Chemokines - biosynthesis; Cockroaches - immunology; Cytokines - biosynthesis; Dendritic Cells - immunology; Feces - chemistry; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; General aspects; Genetics of the immune response; Immunity, Innate; Immunobiology; Inflammation; Lung - cytology; Lung - immunology; Mathematics in biology. Statistical analysis. Models. Metrology. Data processing in biology (general aspects); Mice; Mice, Inbred BALB C; Molecular and cellular biology; Pneumonia - immunology; Research Article; Th17 Cells - immunology; Th2 Cells - immunology; Toll-Like Receptors - metabolism; Europe; Germany; Cockroach; Dendritic cell; Immune response; Pathogen associated-molecular patterns; Cytokines; Airway inflammation; Chemokines; Toll-like receptor; Cytokine; Natural immunity; Toll like receptor; Exposure; Respiratory system; Pathogen Associated Molecular Patterns; Chemokine; Antigen presenting cell; T-Lymphocyte; Environment; Early; Th2 lymphocyte; Th17 lymphocyte
• ISSN: 1662-811X; 1662-8128
• DOI: 10.1159/000320718

Cockroach exposure is a major risk factor for the development of asthma; however, the early immune events induced by cockroach leading to the Th2 response are not fully understood. Exposure of naïve mice to German cockroach (GC) feces (frass) was sufficient to induce dendritic cell (DC) recruiting and activating chemokines C-C motif ligand 20, granulocyte macrophage colony-stimulating factor, granulocyte colony-stimulating factor and macrophage inflammatory protein-1α into the airways. This corresponded with an increase in myeloid DCs (mDCs) in the airways as well as increased expression of CD80 and CD86 on the mDCs. Plasmacytoid DCs in the lung were unchanged. Levels of IL-5, IL-17A and IL-6 cytokines in whole lung cultures were significantly increased 18 h following GC frass exposure demonstrating the early development of a mixed Th2/Th17 response. In addition, GC frass stimulated the production of IL-23, IL-6 and IL-12p70 from bone marrow-derived mDCs. Adoptive transfer of GC frass-pulsed mDCs induced airway reactivity, airway inflammation as well as eosinophilia and induced a strong Th2/Th17 response in the lung. MyD88-deficient bone marrow-derived mDCs did not respond to GC frass treatment, suggesting a functional Toll-like receptor pathway was important to induce the Th2/Th17 response. Together, our data show that GC frass activated the innate immune response to augment DC recruitment and activation of mDCs which promoted robust T cell-skewing cytokines and ultimately drive the development of airway inflammation.