Impaired pneumovax-23-induced monocyte-derived cytokine production in patients with common variable immunodeficiency

J Clin Immunol. 2010 May;30(3):435-41. doi: 10.1007/s10875-010-9371-z. Epub 2010 Feb 23.

Abstract

Introduction: 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.

Findings: 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.

Conclusion: 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.

MeSH terms

  • Animals
  • Antigens, Bacterial / immunology
  • B-Lymphocytes / immunology
  • Bacterial Capsules / immunology
  • Bacterial Vaccines / pharmacology*
  • Cells, Cultured
  • Common Variable Immunodeficiency / complications
  • Common Variable Immunodeficiency / drug therapy
  • Common Variable Immunodeficiency / immunology*
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Humans
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Mice
  • Pneumococcal Infections / etiology
  • Pneumococcal Infections / immunology*
  • Pneumococcal Infections / prevention & control
  • Streptococcus pneumoniae / immunology*
  • T-Lymphocytes / immunology
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / immunology
  • Toll-Like Receptor 2 / metabolism

Substances

  • Antigens, Bacterial
  • Bacterial Vaccines
  • Cytokines
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2