Impaired pneumovax-23-induced monocyte-derived cytokine production in patients with common variable immunodeficiency.
BACKGROUND
Streptococcus pneumoniae is one of the most common infectious pathogens in common variable immunodeficiency (CVID). Both innate and adaptive immune response appears to play a role in defense against S. pneumoniae. In mice, it has been established that TLR2 and macrophages-derived cytokines (IL-6, TNF-alpha) play a crucial role in defense against S. pneumoniae. In humans, monocyte/macrophage-derived cytokines in response to S. pneumoniae have not been studied. Patients with CVID respond poorly to Pneumovax-23 (containing all capsular polysaccharides) vaccination.


RESULTS
In this study, we show that Pneumovax-23, in a concentration and time-dependent manner, induced secretion of IL-6, IL-10, and TNF-alpha by monocytes and not by B cells or T cells from healthy controls. Furthermore, Pneumovax-23-induced secretion of IL-6 and TNF-alpha was significantly less in patients with CVID as compared with controls. In addition, Pneumovax-23-induced upregulation of TLR2 in all four subsets of monocytes; however, differences between control and CVID were not significant.


CONCLUSIONS
Pneumovax-23-induced monocytes-derived cytokine production is impaired in CVID, which may play an important role in increased susceptibility of CVID patients to S. pneumoniae infection.
Hong
Raymond
R
Division of Basic and Clinical Immunology, University of California, Irvine, CA 92697, USA.
Agrawal
Sudhanshu
S
Gollapudi
Sastry
S
Gupta
Sudhir
S
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D016667:Bacterial Capsules / Q000276:immunology; D001428:Bacterial Vaccines / Q000494:pharmacology*; D002478:Cells, Cultured; D017074:Common Variable Immunodeficiency / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D011008:Pneumococcal Infections / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D016207:Cytokines; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2