Borrelia burgdorferi Manipulates Innate and Adaptive Immunity to Establish Persistence in Rodent Reservoir Hosts
Posted: Sun 19 Mar 2017 7:01
The free and full article is here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5316537/Front Immunol. 2017 Feb 20;8:116. doi: 10.3389/fimmu.2017.00116. eCollection 2017.
Borrelia burgdorferi Manipulates Innate and Adaptive Immunity to Establish Persistence in Rodent Reservoir Hosts.
Tracy KE1, Baumgarth N2.
1 Graduate Group in Immunology, University of California Davis, Davis, CA, USA; Center for Comparative Medicine, University of California Davis, Davis, CA, USA.
2 Graduate Group in Immunology, University of California Davis, Davis, CA, USA; Center for Comparative Medicine, University of California Davis, Davis, CA, USA; Department of Pathology, Microbiology and Immunology, University of California Davis, Davis, CA, USA.
Borrelia burgdorferi sensu lato species complex is capable of establishing persistent infections in a wide variety of species, particularly rodents. Infection is asymptomatic or mild in most reservoir host species, indicating successful co-evolution of the pathogen with its natural hosts. However, infected humans and other incidental hosts can develop Lyme disease, a serious inflammatory syndrome characterized by tissue inflammation of joints, heart, muscles, skin, and CNS. Although B. burgdorferi infection induces both innate and adaptive immune responses, they are ultimately ineffective in clearing the infection from reservoir hosts, leading to bacterial persistence. Here, we review some mechanisms by which B. burgdorferi evades the immune system of the rodent host, focusing in particular on the effects of innate immune mechanisms and recent findings suggesting that T-dependent B cell responses are subverted during infection. A better understanding of the mechanisms causing persistence in rodents may help to increase our understanding of the pathogenesis of Lyme disease and ultimately aid in the development of therapies that support effective clearance of the bacterial infection by the host's immune system.
complement inhibition; germinal center; immune evasion; immune exhaustion; lyme disease; persistent infection
PMID: 28265270 PMCID: PMC5316537 DOI: 10.3389/fimmu.2017.00116
Free PMC Article
The phenomena described earlier represent potential novel mechanism(s) for manipulation of the adaptive immune system by a pathogen that establishes persistent infections in its reservoir host. Elucidation of these mechanisms has important translational and clinical applications. A better understanding of how B. burgdorferi persists long term in rodents would be useful for understanding public health risks and devising appropriate preventative measures in endemic areas. Given the extensive similarities in the immune system of rodents and humans, it seems likely that the mechanisms of immune evasion and suppression outlined here may also be active in at least some infected humans. The induction of diseases such as carditis, arthritis, acrodermatitis chronica atrophicans, and neuroborreliosis seen in some patients with Lyme disease and infected companion animals, but rarely in mice, suggest maladaptation of B. burgdorferi to these hosts. Humans developing these inflammatory diseases to B. burgdorferi infection may have an immune system that is ineffectively suppressed by B. burgdorferi. There is good experimental evidence that a block of pro-inflammatory T cell responses, such as facilitated through blockade of IL-12, will cause reductions in arthritis development in C3H mice, but it also causes increases in Borrelia tissue loads (121, 122). Development of therapeutics that can shift the balance toward immune activation and bacterial clearance without causing inflammation-induced diseases might provide superior tools to the current antibiotic therapies.
Much remains to be elucidated about the mechanisms by which Borrelia evades the host response. This area of research provides a particularly rich ground for collaboration among evolutionary biologists, ecologists, microbiologists, and immunologists.