CD14, a key candidate gene associated with a specific immune response to cockroach

Peisong Gao, D. N. Grigoryev, N. M. Rafaels, D. Mu, J. M. Wright, C. Cheadle, A. Togias, Terri L Beaty, Rasika Mathias, John Thomas Schroeder, K. C. Barnes

Research output: Contribution to journalArticle

Abstract

Background Sensitization to cockroach allergen is one of the strongest predictors of asthma morbidity, especially among African Americans. Objective Our aims were to determine the genomic basis of cockroach sensitization and the specific response to cockroach antigen. Methods We investigated the Th1/Th2 cytokine profile of co-cultured plasmacytoid dendritic cells (pDCs) and CD4 + T cells and the 'transcript signature' of the immune response to cockroach antigen using high-throughput expression profiling of co-cultured cells. Results We observed significantly elevated levels of IL-13, IL-10, and TNF-α, but undetectable levels of IL-12p70 and IFN-α, when cultures were exposed to crude cockroach antigen. A significant difference was observed for IL-13 between cockroach-allergic and non-allergic individuals (P=0.039). Microarray analyses demonstrated a greater response at 48 h compared with 4 h, with 50 genes being uniquely expressed in cockroach antigen-treated cells, including CD14, S100A8, CCL8, and IFI44L. The increased CD14 expression was further observed in purified pDCs, human monocytic THP-1 cells, and the supernatant of co-cultured pDCs and CD4+ T cells on exposure to cockroach extract. Furthermore, the most differential expression of CD14 between cockroach allergy and non-cockroach allergy was only observed among individuals with the CC 'high-risk' genotype of the CD14 -260C/T. Ingenuity Pathways Analysis analyses suggested the IFN signalling as the most significant canonical pathway. Conclusion Our results suggest that these differentially expressed genes, particularly CD14, and genes in the IFN signalling pathway may be important candidates for further investigation of their role in the immune response to cockroach allergen.

Original languageEnglish (US)
Pages (from-to)1353-1364
Number of pages12
JournalClinical and Experimental Allergy
Volume40
Issue number9
DOIs
StatePublished - Sep 2010

Fingerprint

Cockroaches
Genes
Dendritic Cells
Antigens
Interleukin-13
Allergens
Hypersensitivity
T-Lymphocytes
Microarray Analysis
African Americans
Interleukin-10
Cultured Cells
Asthma
Genotype
Cytokines
Morbidity

Keywords

  • asthma
  • CD14
  • CD4 T cells
  • cockroach sensitization
  • dendritic cells (DCs)
  • high-throughput expression profiling

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Gao, P., Grigoryev, D. N., Rafaels, N. M., Mu, D., Wright, J. M., Cheadle, C., ... Barnes, K. C. (2010). CD14, a key candidate gene associated with a specific immune response to cockroach. Clinical and Experimental Allergy, 40(9), 1353-1364. https://doi.org/10.1111/j.1365-2222.2010.03561.x

CD14, a key candidate gene associated with a specific immune response to cockroach. / Gao, Peisong; Grigoryev, D. N.; Rafaels, N. M.; Mu, D.; Wright, J. M.; Cheadle, C.; Togias, A.; Beaty, Terri L; Mathias, Rasika; Schroeder, John Thomas; Barnes, K. C.

In: Clinical and Experimental Allergy, Vol. 40, No. 9, 09.2010, p. 1353-1364.

Research output: Contribution to journalArticle

Gao, Peisong ; Grigoryev, D. N. ; Rafaels, N. M. ; Mu, D. ; Wright, J. M. ; Cheadle, C. ; Togias, A. ; Beaty, Terri L ; Mathias, Rasika ; Schroeder, John Thomas ; Barnes, K. C. / CD14, a key candidate gene associated with a specific immune response to cockroach. In: Clinical and Experimental Allergy. 2010 ; Vol. 40, No. 9. pp. 1353-1364.
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AU - Grigoryev, D. N.

AU - Rafaels, N. M.

AU - Mu, D.

AU - Wright, J. M.

AU - Cheadle, C.

AU - Togias, A.

AU - Beaty, Terri L

AU - Mathias, Rasika

AU - Schroeder, John Thomas

AU - Barnes, K. C.

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N2 - Background Sensitization to cockroach allergen is one of the strongest predictors of asthma morbidity, especially among African Americans. Objective Our aims were to determine the genomic basis of cockroach sensitization and the specific response to cockroach antigen. Methods We investigated the Th1/Th2 cytokine profile of co-cultured plasmacytoid dendritic cells (pDCs) and CD4 + T cells and the 'transcript signature' of the immune response to cockroach antigen using high-throughput expression profiling of co-cultured cells. Results We observed significantly elevated levels of IL-13, IL-10, and TNF-α, but undetectable levels of IL-12p70 and IFN-α, when cultures were exposed to crude cockroach antigen. A significant difference was observed for IL-13 between cockroach-allergic and non-allergic individuals (P=0.039). Microarray analyses demonstrated a greater response at 48 h compared with 4 h, with 50 genes being uniquely expressed in cockroach antigen-treated cells, including CD14, S100A8, CCL8, and IFI44L. The increased CD14 expression was further observed in purified pDCs, human monocytic THP-1 cells, and the supernatant of co-cultured pDCs and CD4+ T cells on exposure to cockroach extract. Furthermore, the most differential expression of CD14 between cockroach allergy and non-cockroach allergy was only observed among individuals with the CC 'high-risk' genotype of the CD14 -260C/T. Ingenuity Pathways Analysis analyses suggested the IFN signalling as the most significant canonical pathway. Conclusion Our results suggest that these differentially expressed genes, particularly CD14, and genes in the IFN signalling pathway may be important candidates for further investigation of their role in the immune response to cockroach allergen.

AB - Background Sensitization to cockroach allergen is one of the strongest predictors of asthma morbidity, especially among African Americans. Objective Our aims were to determine the genomic basis of cockroach sensitization and the specific response to cockroach antigen. Methods We investigated the Th1/Th2 cytokine profile of co-cultured plasmacytoid dendritic cells (pDCs) and CD4 + T cells and the 'transcript signature' of the immune response to cockroach antigen using high-throughput expression profiling of co-cultured cells. Results We observed significantly elevated levels of IL-13, IL-10, and TNF-α, but undetectable levels of IL-12p70 and IFN-α, when cultures were exposed to crude cockroach antigen. A significant difference was observed for IL-13 between cockroach-allergic and non-allergic individuals (P=0.039). Microarray analyses demonstrated a greater response at 48 h compared with 4 h, with 50 genes being uniquely expressed in cockroach antigen-treated cells, including CD14, S100A8, CCL8, and IFI44L. The increased CD14 expression was further observed in purified pDCs, human monocytic THP-1 cells, and the supernatant of co-cultured pDCs and CD4+ T cells on exposure to cockroach extract. Furthermore, the most differential expression of CD14 between cockroach allergy and non-cockroach allergy was only observed among individuals with the CC 'high-risk' genotype of the CD14 -260C/T. Ingenuity Pathways Analysis analyses suggested the IFN signalling as the most significant canonical pathway. Conclusion Our results suggest that these differentially expressed genes, particularly CD14, and genes in the IFN signalling pathway may be important candidates for further investigation of their role in the immune response to cockroach allergen.

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