Antibody-mediated immunity to the obligate intracellular bacterial pathogen Coxiella burnetii is Fc receptor- and complement-independent

Jeffrey G Shannon,Robert A Heinzen,Diane C Cockrell,Gregory L Stahl,Kazue Takahashi

doi:10.1186/1471-2172-10-26

Abstract

BackgroundThe 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 naïve 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.ResultsVirulent 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 naïve 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.ConclusionDespite 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.

Highlights

The obligate intracellular bacterial pathogen Coxiella burnetii causes the zoonosis Q fever
We determined whether Ab opsonization http://www.biomedcentral.com/1471-2172/10/26 affects replication in human macrophages (MΦ), an in vitro model of C. burnetii infection [18]
Burnetii that had been incubated with naïve human serum or immune serum from a chronic Q fever patient containing high titers of anti-C. burnetii antibodies and measured bacterial replication over 6 days by quantitative PCR

Summary

Introduction

The obligate intracellular bacterial pathogen Coxiella burnetii causes the zoonosis Q fever. Passive immunization with immune serum can protect naïve animals from challenge with virulent C. burnetii, indicating a role for antibody (Ab) in protection. The mechanism of this Ab-mediated protection is unknown. Coxiella burnetii is an obligate intracellular bacterium that causes the zoonotic disease Q fever. One dose of Q-vax provides long-lived protective immunity [4]. This vaccine can cause severe side effects in recipients with previous exposure to C. burnetii necessitating skin testing to determine the immune status of potential vaccinees prior to vaccination. There is a clear need for a safe, effective subunit vaccine that eliminates the need for pre-testing

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