PMID- 19426498 OWN - NLM STAT- MEDLINE DCOM- 20090709 LR - 20211020 IS - 1471-2172 (Electronic) IS - 1471-2172 (Linking) VI - 10 DP - 2009 May 8 TI - Antibody-mediated immunity to the obligate intracellular bacterial pathogen Coxiella burnetii is Fc receptor- and complement-independent. PG - 26 LID - 10.1186/1471-2172-10-26 [doi] AB - BACKGROUND: The obligate intracellular bacterial pathogen Coxiella burnetii causes the zoonosis Q fever. The intracellular niche of C. burnetii has led to the assumption that cell-mediated immunity is the most important immune component for protection against this pathogen. However, passive immunization with immune serum can protect naive animals from challenge with virulent C. burnetii, indicating a role for antibody (Ab) in protection. The mechanism of this Ab-mediated protection is unknown. Therefore, we conducted a study to determine whether Fc receptors (FcR) or complement contribute to Ab-mediated immunity (AMI) to C. burnetii. RESULTS: Virulent C. burnetii infects and replicates within human dendritic cells (DC) without inducing their maturation or activation. We investigated the effects of Ab opsonized C. burnetii on human monocyte-derived and murine bone marrow-derived DC. Infection of DC with Ab-opsonized C. burnetii resulted in increased expression of maturation markers and inflammatory cytokine production. Bacteria that had been incubated with naive serum had minimal effect on DC, similar to virulent C. burnetii alone. The effect of Ab opsonized C. burnetii on DC was FcR dependent as evidenced by a reduced response of DC from FcR knockout (FcR k/o) compared to C57Bl/6 (B6) mice. To address the potential role of FcR in Ab-mediated protection in vivo, we compared the response of passively immunized FcR k/o mice to the B6 controls. Interestingly, we found that FcR are not essential for AMI to C. burnetii in vivo. We subsequently examined the role of complement in AMI by passively immunizing and challenging several different strains of complement-deficient mice and found that AMI to C. burnetii is also complement-independent. CONCLUSION: Despite our data showing FcR-dependent stimulation of DC in vitro, Ab-mediated immunity to C. burnetii in vivo is FcR-independent. We also found that passive immunity to this pathogen is independent of complement. FAU - Shannon, Jeffrey G AU - Shannon JG AD - Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA. jshannon@niaid.nih.gov FAU - Cockrell, Diane C AU - Cockrell DC FAU - Takahashi, Kazue AU - Takahashi K FAU - Stahl, Gregory L AU - Stahl GL FAU - Heinzen, Robert A AU - Heinzen RA LA - eng GR - R01 HL052886/HL/NHLBI NIH HHS/United States GR - P01 AI052343/AI/NIAID NIH HHS/United States GR - P50 DE016191/DE/NIDCR NIH HHS/United States GR - DE016191/DE/NIDCR NIH HHS/United States GR - HL52886/HL/NHLBI NIH HHS/United States GR - ImNIH/Intramural NIH HHS/United States GR - HL56068/HL/NHLBI NIH HHS/United States GR - DE017821/DE/NIDCR NIH HHS/United States GR - AI052343/AI/NIAID NIH HHS/United States GR - R01 DE017821/DE/NIDCR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural DEP - 20090508 PL - England TA - BMC Immunol JT - BMC immunology JID - 100966980 RN - 0 (Antigen-Antibody Complex) RN - 0 (Antigens, Bacterial) RN - 0 (Immunoglobulin G) RN - 0 (Receptors, Fc) RN - 9007-36-7 (Complement System Proteins) SB - IM MH - Animals MH - Antibody-Dependent Cell Cytotoxicity MH - Antigen-Antibody Complex/immunology/metabolism MH - Antigens, Bacterial/immunology MH - Cell Differentiation/genetics/immunology MH - Complement Activation/genetics/immunology MH - Complement System Proteins/genetics/*metabolism MH - Coxiella burnetii/*immunology MH - Dendritic Cells/immunology/*metabolism/microbiology/pathology MH - Immunization, Passive MH - Immunoglobulin G/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Q Fever/immunology MH - Receptors, Fc/genetics/*metabolism PMC - PMC2689861 EDAT- 2009/05/12 09:00 MHDA- 2009/07/10 09:00 PMCR- 2009/05/08 CRDT- 2009/05/12 09:00 PHST- 2008/11/28 00:00 [received] PHST- 2009/05/08 00:00 [accepted] PHST- 2009/05/12 09:00 [entrez] PHST- 2009/05/12 09:00 [pubmed] PHST- 2009/07/10 09:00 [medline] PHST- 2009/05/08 00:00 [pmc-release] AID - 1471-2172-10-26 [pii] AID - 10.1186/1471-2172-10-26 [doi] PST - epublish SO - BMC Immunol. 2009 May 8;10:26. doi: 10.1186/1471-2172-10-26.