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Natural IgG antibodies provide innate protection against ficolin-opsonized bacteria.

ABSTRACT: For nearly five decades since its discovery, the role of natural IgG, which pre-exists in neonates and uninfected individuals, has remained unclear due to the general perception that natural antibodies lack affinity for pathogens. Here, we show for the first time that natural IgG recognizes a spectrum of bacteria through lectins like ficolin and mannose binding lectin (MBL). Infection-inflammation condition markedly increased the affinity of natural IgG for bacteria associated with ficolins. After opsonization with IgG:ficolin complex, the bacteria were phagocytosed by monocytes via Fc?RI. Infection of C3(-/-) mice indicated that the natural IgG-mediated immune complex was formed independently of C3. AID(-/-) mice lacking IgG were susceptible to infection, unless reconstituted with natural IgG. Thus, we have proven that natural IgG is not quiescent; rather, it plays a vital and immediate role in immune defense. Our findings provide a fresh perspective on natural antibodies, opening new avenues to explore host-microbe interaction.

SUBMITTER: Panda S

PROVIDER: S-EPMC3831310 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Natural IgG antibodies provide innate protection against ficolin-opsonized bacteria.

Panda Saswati S Zhang Jing J Tan Nguan Soon NS Ho Bow B Ding Jeak Ling JL

The EMBO journal 20130903 22

For nearly five decades since its discovery, the role of natural IgG, which pre-exists in neonates and uninfected individuals, has remained unclear due to the general perception that natural antibodies lack affinity for pathogens. Here, we show for the first time that natural IgG recognizes a spectrum of bacteria through lectins like ficolin and mannose binding lectin (MBL). Infection-inflammation condition markedly increased the affinity of natural IgG for bacteria associated with ficolins. Aft ...[more]

PMID: 24002211

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Project description:Multistrain microbial pathogens often induce strain-specific antibody responses in their vertebrate hosts. Mothers can transmit antibodies to their offspring, which can provide short-term, strain-specific protection against infection. Few experimental studies have investigated this phenomenon for multiple strains of zoonotic pathogens occurring in wildlife reservoir hosts. The tick-borne bacterium Borrelia afzelii causes Lyme disease in Europe and consists of multiple strains that cycle between the tick vector (Ixodes ricinus) and vertebrate hosts, such as the bank vole (Myodes glareolus). We used a controlled experiment to show that female bank voles infected with B. afzelii via tick bite transmit protective antibodies to their offspring. To test the specificity of protection, the offspring were challenged using a natural tick bite challenge with either the maternal strain to which the mothers had been exposed or a different strain. The maternal antibodies protected the offspring against a homologous infectious challenge but not against a heterologous infectious challenge. The offspring from the uninfected control mothers were equally susceptible to both strains. Borrelia outer surface protein C (OspC) is an antigen that is known to induce strain-specific immunity. Maternal antibodies in the offspring reacted more strongly with homologous than with heterologous recombinant OspC, but other antigens may also mediate strain-specific immunity. Our study shows that maternal antibodies provide strain-specific protection against B. afzelii in an ecologically important rodent reservoir host. The transmission of maternal antibodies may have important consequences for the epidemiology of multistrain pathogens in nature.IMPORTANCE Many microbial pathogen populations consist of multiple strains that induce strain-specific antibody responses in their vertebrate hosts. Females can transmit these antibodies to their offspring, thereby providing them with short-term strain-specific protection against microbial pathogens. We investigated this phenomenon using multiple strains of the tick-borne microbial pathogen Borrelia afzelii and its natural rodent reservoir host, the bank vole, as a model system. We found that female bank voles infected with B. afzelii transmitted to their offspring maternal antibodies that provided highly efficient but strain-specific protection against a natural tick bite challenge. The transgenerational transfer of antibodies could be a mechanism that maintains the high strain diversity of this tick-borne pathogen in nature.

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Natural IgG antibodies provide innate protection against ficolin-opsonized bacteria.

Publications

Natural IgG antibodies provide innate protection against ficolin-opsonized bacteria.

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