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Characterization of Stress and Innate Immunity Resistance of Wild-Type and ?p66 Borrelia burgdorferi.


ABSTRACT: Borrelia burgdorferi is a causative agent of Lyme disease, the most common arthropod-borne disease in the United States. B. burgdorferi evades host immune defenses to establish a persistent, disseminated infection. Previous work showed that P66-deficient B. burgdorferi (?p66) is cleared quickly after inoculation in mice. We demonstrate that the ?p66 strain is rapidly cleared from the skin inoculation site prior to dissemination. The rapid clearance of ?p66 bacteria is not due to inherent defects in multiple properties that might affect infectivity: bacterial outer membrane integrity, motility, chemotactic response, or nutrient acquisition. This led us to the hypothesis that P66 has a role in mouse cathelicidin-related antimicrobial peptide (mCRAMP; a major skin antimicrobial peptide) and/or neutrophil evasion. Neither wild-type (WT) nor ?p66 B. burgdorferi was susceptible to mCRAMP. To examine the role of neutrophil evasion, we administered neutrophil-depleting antibody anti-Ly6G (1A8) to C3H/HeN mice and subsequently monitored the course of B. burgdorferi infection. ?p66 mutants were unable to establish infection in neutrophil-depleted mice, suggesting that the important role of P66 during early infection is through another mechanism. Neutrophil depletion did not affect WT B. burgdorferi bacterial burdens in the skin (inoculation site), ear, heart, or tibiotarsal joint at early time points postinoculation. This was unexpected given that prior in vitro studies demonstrated neutrophils phagocytose and kill B. burgdorferi These data, together with our previous work, suggest that despite the in vitro ability of host innate defenses to kill B. burgdorferi, individual innate immune mechanisms have limited contributions to controlling early B. burgdorferi infection in the laboratory model used.

SUBMITTER: Curtis MW 

PROVIDER: S-EPMC5778354 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Characterization of Stress and Innate Immunity Resistance of Wild-Type and Δ<i>p66 Borrelia burgdorferi</i>.

Curtis Michael W MW   Hahn Beth L BL   Zhang Kai K   Li Chunhao C   Robinson Richard T RT   Coburn Jenifer J  

Infection and immunity 20180122 2


<i>Borrelia burgdorferi</i> is a causative agent of Lyme disease, the most common arthropod-borne disease in the United States. <i>B. burgdorferi</i> evades host immune defenses to establish a persistent, disseminated infection. Previous work showed that P66-deficient <i>B. burgdorferi</i> (Δ<i>p66</i>) is cleared quickly after inoculation in mice. We demonstrate that the Δ<i>p66</i> strain is rapidly cleared from the skin inoculation site prior to dissemination. The rapid clearance of Δ<i>p66</  ...[more]

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