A human monoclonal immunoglobulin M reduces bacteremia and inflammation in a mouse model of systemic pneumococcal infection

Kevin Fabrizio, Abraham Groner, Marianne Boes, Liise-anne Pirofski

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Antibody-based approaches to pneumococcal disease may hold promise for immunocompromised patients in whom vaccines are less immunogenic and/or in the context of antimicrobial resistance. Antibody-mediated protection against experimental pneumococcal pneumonia has been shown to depend on immunoregulation, but the relationship between antibody and protection against pneumococcal sepsis and immunoregulation has not been examined. Similarly, the requirement for B and T cells for antibody efficacy is not known. In this study, we determined the efficacy of the human pneumococcal capsular polysaccharide serotype 3-specific antibody, A7 (immunoglobulin M [IgM]), in secretory IgM (sIgM)-/-, CD4-/-, CD8-/_, μMT -/_, and SCID mice and investigated its effect on cytokine and chemokine expression in sera and spleens from mice with intact cellular immunity. A7 is known to be protective against systemic infection with serotype 3 and to require complement for efficacy. Compared to that of an isotype control antibody, A7 administration prolonged the survival of mice of each immunodeficient strain and was associated with a significant reduction in CFU in blood, lung, and spleen samples and a significantly reduced level of keratinocyte-derived chemokine (KC), interleukin-6 (IL-6), and macrophage inflammatory protein-2 (MIP-2) expression in normal and sIgM-/- mice. Studies with mice treated with penicillin revealed similar reductions in CFU and similar levels of IL-6, KC, or MIP-2 expression in A7- and penicillin-treated mice. These findings demonstrate that natural IgM and B and T cells are dispensable for A7-mediated protection against experimental pneumococcal sepsis and suggest that the efficacy of antibody-mediated protection depends on immunomodulation. Taken together, our data extend the association between antibody-mediated protection and immunomodulation to protection against systemic pneumococcal infection and to a clinically important serotype often responsible for pneumococcal sepsis.

Original languageEnglish (US)
Pages (from-to)382-390
Number of pages9
JournalClinical and Vaccine Immunology
Volume14
Issue number4
DOIs
StatePublished - Apr 2007

Fingerprint

Pneumococcal Infections
Bacteremia
Immunoglobulin M
Inflammation
Antibodies
Chemokine CXCL2
Sepsis
T-cells
Immunomodulation
Penicillins
Interleukin-6
B-Lymphocytes
Spleen
Pneumococcal Pneumonia
T-Lymphocytes
SCID Mice
Immunocompromised Host
Chemokines
Cellular Immunity
Polysaccharides

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Immunology
  • Immunology and Allergy
  • Microbiology (medical)

Cite this

A human monoclonal immunoglobulin M reduces bacteremia and inflammation in a mouse model of systemic pneumococcal infection. / Fabrizio, Kevin; Groner, Abraham; Boes, Marianne; Pirofski, Liise-anne.

In: Clinical and Vaccine Immunology, Vol. 14, No. 4, 04.2007, p. 382-390.

Research output: Contribution to journalArticle

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