Faculty Collaboration Database

Characterization of Stress and Innate Immunity Resistance of Wild-Type and Δp66 Borrelia burgdorferi. Infect Immun 2018 Feb;86(2)

Date

11/22/2017

Pubmed ID

29158430

Pubmed Central ID

PMC5778354

DOI

10.1128/IAI.00186-17

Scopus ID

2-s2.0-85040966556 (requires institutional sign-in at Scopus site)   10 Citations

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 (Δp66) is cleared quickly after inoculation in mice. We demonstrate that the Δp66 strain is rapidly cleared from the skin inoculation site prior to dissemination. The rapid clearance of Δp66 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 Δp66 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. Δp66 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.

Author List

Curtis MW, Hahn BL, Zhang K, Li C, Robinson RT, Coburn J

Author

Jenifer Coburn PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Bacterial Proteins
Borrelia burgdorferi
Disease Models, Animal
Female
Gene Deletion
Immunity, Innate
Lyme Disease
Mice, Inbred C3H
Neutrophils
Porins