Impaired phenotype and function of monocyte derived dendritic cells in pulmonary tuberculosis
Summary Pulmonary tuberculosis (PTB) is often associated with impaired immunological functions. Blood monocytes, which can differentiate into dendritic cells upon cytokine stimulation, play a central role in adequate immune reactivity. Here, we investigated the morphologic, phenotypic and functional...
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| Veröffentlicht in: | Tuberculosis (Edinburgh, Scotland) Scotland), 2009-01, Vol.89 (1), p.77-83 |
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| creator | Rajashree, P Krishnan, Gokula Das, Sulochana D |
| description | Summary Pulmonary tuberculosis (PTB) is often associated with impaired immunological functions. Blood monocytes, which can differentiate into dendritic cells upon cytokine stimulation, play a central role in adequate immune reactivity. Here, we investigated the morphologic, phenotypic and functional characteristics of in vitro-generated monocyte derived dendritic cells (MoDC) from PTB patients in comparison with healthy subjects. Phenotypic analysis revealed a defective differentiation of MoDC in PTB patients as assessed by a strong down regulation of CD1a, MHC II, CD80 and CD83 expression and impaired allostimulatory function under the influence of IL-4 and GM-CSF. In contrast, the expression of CD86 was not affected and remained same as in healthy subjects. Furthermore, the maturation status of lipopolysaccharide (LPS) stimulated MoDC was not optimal in PTB. However, the MoDC of PTB patients produced significantly higher levels of TNF-α and IL-6 but lower levels of IL-12 compared to healthy subjects. These findings suggest that there is a fundamental defect in the differentiation and maturation of dendritic cells during PTB that may compromise the antigen presentation and subsequent immune functions. |
| doi_str_mv | 10.1016/j.tube.2008.07.006 |
| format | Article |
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Blood monocytes, which can differentiate into dendritic cells upon cytokine stimulation, play a central role in adequate immune reactivity. Here, we investigated the morphologic, phenotypic and functional characteristics of in vitro-generated monocyte derived dendritic cells (MoDC) from PTB patients in comparison with healthy subjects. Phenotypic analysis revealed a defective differentiation of MoDC in PTB patients as assessed by a strong down regulation of CD1a, MHC II, CD80 and CD83 expression and impaired allostimulatory function under the influence of IL-4 and GM-CSF. In contrast, the expression of CD86 was not affected and remained same as in healthy subjects. Furthermore, the maturation status of lipopolysaccharide (LPS) stimulated MoDC was not optimal in PTB. However, the MoDC of PTB patients produced significantly higher levels of TNF-α and IL-6 but lower levels of IL-12 compared to healthy subjects. 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Blood monocytes, which can differentiate into dendritic cells upon cytokine stimulation, play a central role in adequate immune reactivity. Here, we investigated the morphologic, phenotypic and functional characteristics of in vitro-generated monocyte derived dendritic cells (MoDC) from PTB patients in comparison with healthy subjects. Phenotypic analysis revealed a defective differentiation of MoDC in PTB patients as assessed by a strong down regulation of CD1a, MHC II, CD80 and CD83 expression and impaired allostimulatory function under the influence of IL-4 and GM-CSF. In contrast, the expression of CD86 was not affected and remained same as in healthy subjects. Furthermore, the maturation status of lipopolysaccharide (LPS) stimulated MoDC was not optimal in PTB. However, the MoDC of PTB patients produced significantly higher levels of TNF-α and IL-6 but lower levels of IL-12 compared to healthy subjects. These findings suggest that there is a fundamental defect in the differentiation and maturation of dendritic cells during PTB that may compromise the antigen presentation and subsequent immune functions.</description><subject>Adult</subject><subject>Antigen Presentation</subject><subject>Antigens, CD - immunology</subject><subject>Antigens, CD1 - immunology</subject><subject>B7-1 Antigen - immunology</subject><subject>B7-2 Antigen - immunology</subject><subject>Case-Control Studies</subject><subject>CD83 Antigen</subject><subject>Cell Differentiation</subject><subject>Cells, Cultured</subject><subject>Cytokines - biosynthesis</subject><subject>Cytokines - immunology</subject><subject>Dendritic cells</subject><subject>Dendritic Cells - cytology</subject><subject>Dendritic Cells - immunology</subject><subject>Differentiation</subject><subject>Female</subject><subject>Granulocyte-Macrophage Colony-Stimulating Factor - immunology</subject><subject>Humans</subject><subject>Immunoglobulins - immunology</subject><subject>Infectious Disease</subject><subject>Interleukin-12 - immunology</subject><subject>Interleukin-4 - immunology</subject><subject>Interleukin-6 - immunology</subject><subject>Lipopolysaccharide</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Male</subject><subject>Maturation</subject><subject>Membrane Glycoproteins - immunology</subject><subject>Middle Aged</subject><subject>Mycobacterium</subject><subject>Mycobacterium tuberculosis</subject><subject>Phenotype</subject><subject>Pulmonary tuberculosis</subject><subject>Pulmonary/Respiratory</subject><subject>Statistics, Nonparametric</subject><subject>T-Lymphocytes - immunology</subject><subject>Tuberculosis, Pulmonary - immunology</subject><subject>Tumor Necrosis Factor-alpha - immunology</subject><subject>Young Adult</subject><issn>1472-9792</issn><issn>1873-281X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUGL1TAUhYMozjj6B1xIVu5ab9I2SUEEGdQZGHChghsJbXKDebZJTdqB9-9NeQ8EF-MqWXzncM85hLxkUDNg4s2hXrcRaw6gapA1gHhELpmSTcUV-_64_FvJq172_II8y_kARQQKnpILphRvFIdL8uN2Xgaf0NLlJ4a4HhekQ7DUbcGsPgYaHZ1jiOa4IrWY_H1BLQab_OoNNThNmfpAl20q2JCOdL8pmW2K2efn5Ikbpowvzu8V-fbxw9frm-ru86fb6_d3lWlbWCsHHRfjiMzYBkfeMTd2iGZABS2XhvPGCTn0o3FKWKsGYO3YyU46ZRgXrWmuyOuT75Li7w3zqmef99uGgHHLWgjFWFsy_w_k0PRM9LKA_ASaFHNO6PSS_FzyaQZ6b18f9J5U7-1rkLq0X0Svzu7bOKP9KznXXYC3JwBLGfcek87GYzBoywRm1Tb6h_3f_SM3kw_eDNMvPGI-xC2FUrNmOnMN-su-_z5_GR1ASt78ASgVrSs</recordid><startdate>20090101</startdate><enddate>20090101</enddate><creator>Rajashree, P</creator><creator>Krishnan, Gokula</creator><creator>Das, Sulochana D</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T5</scope><scope>C1K</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20090101</creationdate><title>Impaired phenotype and function of monocyte derived dendritic cells in pulmonary tuberculosis</title><author>Rajashree, P ; Krishnan, Gokula ; Das, Sulochana D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-f0526bbe1cd3eb251fb5eecae80427c223f67a9bcf86dd8a014b5757f8c1264c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adult</topic><topic>Antigen Presentation</topic><topic>Antigens, CD - immunology</topic><topic>Antigens, CD1 - immunology</topic><topic>B7-1 Antigen - immunology</topic><topic>B7-2 Antigen - immunology</topic><topic>Case-Control Studies</topic><topic>CD83 Antigen</topic><topic>Cell Differentiation</topic><topic>Cells, Cultured</topic><topic>Cytokines - biosynthesis</topic><topic>Cytokines - immunology</topic><topic>Dendritic cells</topic><topic>Dendritic Cells - cytology</topic><topic>Dendritic Cells - immunology</topic><topic>Differentiation</topic><topic>Female</topic><topic>Granulocyte-Macrophage Colony-Stimulating Factor - immunology</topic><topic>Humans</topic><topic>Immunoglobulins - immunology</topic><topic>Infectious Disease</topic><topic>Interleukin-12 - immunology</topic><topic>Interleukin-4 - immunology</topic><topic>Interleukin-6 - immunology</topic><topic>Lipopolysaccharide</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Male</topic><topic>Maturation</topic><topic>Membrane Glycoproteins - immunology</topic><topic>Middle Aged</topic><topic>Mycobacterium</topic><topic>Mycobacterium tuberculosis</topic><topic>Phenotype</topic><topic>Pulmonary tuberculosis</topic><topic>Pulmonary/Respiratory</topic><topic>Statistics, Nonparametric</topic><topic>T-Lymphocytes - immunology</topic><topic>Tuberculosis, Pulmonary - immunology</topic><topic>Tumor Necrosis Factor-alpha - immunology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rajashree, P</creatorcontrib><creatorcontrib>Krishnan, Gokula</creatorcontrib><creatorcontrib>Das, Sulochana D</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Tuberculosis (Edinburgh, Scotland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rajashree, P</au><au>Krishnan, Gokula</au><au>Das, Sulochana D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impaired phenotype and function of monocyte derived dendritic cells in pulmonary tuberculosis</atitle><jtitle>Tuberculosis (Edinburgh, Scotland)</jtitle><addtitle>Tuberculosis (Edinb)</addtitle><date>2009-01-01</date><risdate>2009</risdate><volume>89</volume><issue>1</issue><spage>77</spage><epage>83</epage><pages>77-83</pages><issn>1472-9792</issn><eissn>1873-281X</eissn><abstract>Summary Pulmonary tuberculosis (PTB) is often associated with impaired immunological functions. Blood monocytes, which can differentiate into dendritic cells upon cytokine stimulation, play a central role in adequate immune reactivity. Here, we investigated the morphologic, phenotypic and functional characteristics of in vitro-generated monocyte derived dendritic cells (MoDC) from PTB patients in comparison with healthy subjects. Phenotypic analysis revealed a defective differentiation of MoDC in PTB patients as assessed by a strong down regulation of CD1a, MHC II, CD80 and CD83 expression and impaired allostimulatory function under the influence of IL-4 and GM-CSF. In contrast, the expression of CD86 was not affected and remained same as in healthy subjects. Furthermore, the maturation status of lipopolysaccharide (LPS) stimulated MoDC was not optimal in PTB. However, the MoDC of PTB patients produced significantly higher levels of TNF-α and IL-6 but lower levels of IL-12 compared to healthy subjects. These findings suggest that there is a fundamental defect in the differentiation and maturation of dendritic cells during PTB that may compromise the antigen presentation and subsequent immune functions.</abstract><cop>Scotland</cop><pub>Elsevier Ltd</pub><pmid>18823820</pmid><doi>10.1016/j.tube.2008.07.006</doi><tpages>7</tpages></addata></record> |
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| subjects | Adult Antigen Presentation Antigens, CD - immunology Antigens, CD1 - immunology B7-1 Antigen - immunology B7-2 Antigen - immunology Case-Control Studies CD83 Antigen Cell Differentiation Cells, Cultured Cytokines - biosynthesis Cytokines - immunology Dendritic cells Dendritic Cells - cytology Dendritic Cells - immunology Differentiation Female Granulocyte-Macrophage Colony-Stimulating Factor - immunology Humans Immunoglobulins - immunology Infectious Disease Interleukin-12 - immunology Interleukin-4 - immunology Interleukin-6 - immunology Lipopolysaccharide Lipopolysaccharides - pharmacology Male Maturation Membrane Glycoproteins - immunology Middle Aged Mycobacterium Mycobacterium tuberculosis Phenotype Pulmonary tuberculosis Pulmonary/Respiratory Statistics, Nonparametric T-Lymphocytes - immunology Tuberculosis, Pulmonary - immunology Tumor Necrosis Factor-alpha - immunology Young Adult |
| title | Impaired phenotype and function of monocyte derived dendritic cells in pulmonary tuberculosis |
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