Spirochetal Lipoproteins and Immune Evasion

Christodoulides, Alexei; Boyadjian, Ani; Kelesidis, Theodoros

doi:10.3389/fimmu.2017.00364

Cited by 15 publications

(14 citation statements)

References 157 publications

(110 reference statements)

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“…Borrelia spp. possess an arsenal of lipoproteins that aid in mammalian persistence ( Christodoulides et al, 2017 ). Borrelia lipoproteins are immunogenic and must be tightly regulated by environmental cues, including temperature, CO 2 levels and immune pressure ( Brandt et al, 1990 ; Schwan et al, 1995 ; Liang et al, 2004 ; Hyde et al, 2007 ; Wilder et al, 2016 ).…”

Section: Immune Evasion and Disease Severitymentioning

confidence: 99%

Lipid hijacking: A unifying theme in vector-borne diseases

O’Neal

Butler

Rolandelli

et al. 2020

eLife

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Vector-borne illnesses comprise a significant portion of human maladies, representing 17% of global infections. Transmission of vector-borne pathogens to mammals primarily occurs by hematophagous arthropods. It is speculated that blood may provide a unique environment that aids in the replication and pathogenesis of these microbes. Lipids and their derivatives are one component enriched in blood and are essential for microbial survival. For instance, the malarial parasite Plasmodium falciparum and the Lyme disease spirochete Borrelia burgdorferi, among others, have been shown to scavenge and manipulate host lipids for structural support, metabolism, replication, immune evasion, and disease severity. In this Review, we will explore the importance of lipid hijacking for the growth and persistence of these microbes in both mammalian hosts and arthropod vectors.

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Section: Immune Evasion and Disease Severitymentioning

confidence: 99%

Lipid hijacking: A unifying theme in vector-borne diseases

O’Neal

Butler

Rolandelli

et al. 2020

eLife

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“…It is estimated that phase switching occurs at a frequency of around 10 -3 per CFU per generation ( Rosengarten and Wise, 1990 ). In having the ability to undergo phase variation, mycoplasmas are able to evade host immune responses and indeed lead to chronic infections, similar to how Spirochetes might also use antigenic variation in order to establish a chronic infection ( Chambaud et al, 1999 ; Christodoulides et al, 2017 ). Thus, Mycoplasmal lipoproteins have pleotropic immunomodulatory effects and their mechanisms of actions need to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

The Role of Lipoproteins in Mycoplasma-Mediated Immunomodulation

et al. 2018

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Mycoplasma infections, such as walking pneumonia or pelvic inflammatory diseases, are a major threat to public health. Despite their relatively small physical and genomic size, mycoplasmas are known to elicit strong host immune responses, generally inflammatory, while also being able to evade the immune system. The mycoplasma membrane is composed of approximately two-thirds protein and one-third lipid and contains several lipoproteins that are known to regulate host immune responses. Herein, the immunomodulatory effects of mycoplasma lipoproteins are reviewed. A better understanding of the immunomodulatory effects, both activating and evasive, of Mycoplasma surface lipoproteins will contribute to understanding mechanisms potentially relevant to mycoplasma disease vaccine development and treatment.

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“…Neutrophils are major phagocytic cells that utilize a combination of reactive oxygen species (ROS), cytotoxic granules, antimicrobial peptides and Neutrophil Extracellular Traps (NETs) to kill and degrade the invading pathogen 17,18 . However, pathogens have devised several strategies to escape from host innate immune defences mainly through mechanism mediated by their surface proteins 19,20 . These proteins may be pro-inflammatory where they can activate APCs like macrophages and DCs but might also enable the pathogen to avoid recognition through innate receptors (TLRs) by downregulating their expression or causing antigenic variations to evade from host defences 21–24 .…”

Section: Introductionmentioning

confidence: 99%

Deciphering the role of Leptospira surface protein LigA in modulating the host innate immune response

Kumar

Varma

Kavela

et al. 2020

Preprint

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Leptospira, a zoonotic pathogen is known to infect a variety of hosts and capable of establishing persistent infection. This remarkable ability of bacteria is attributed to its potential to evade or modulate the host immune response by exploiting its surface proteins. We have identified and characterized the domain of Leptospira immunoglobulin-like protein A (LigA) that is involved in modulating the host innate immune response. We identified that the 11th domain (A11) of the variable region of LigA (LAV) induces strong TLR4 dependent innate response in mouse macrophages via signalling through MAP kinase pathway leading to the production of pro-inflammatory cytokines (IL-6 and TNF-α) and expression of costimulatory molecules (CD80, CD86, CD40) and maturation marker (MHC-II). A11 is also involved in acquiring complement regulators like FH, C4b binding protein and Plasminogen and mediating functional activity to escape from both classical and alternate pathways of complement-mediated killing. The deletion of A11 significantly impaired TLR4 signalling and subsequent activation of innate immune cells and also inhibited the binding of complement regulators leading to the killing of bacteria. Our study discovered an unprecedented role of LAV as nuclease capable of degrading Neutrophil Extracellular Traps (NETs). This nuclease activity was mediated by A11 and was inhibited with anti-LAV antibodies. These results highlight the moonlighting function of LigA and demonstrates that a single domain of a surface protein is involved in evading a myriad of host innate immune defences, which might allow the persistence of Leptospira in different hosts for a long term without clearance.

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Spirochetal Lipoproteins and Immune Evasion

Cited by 15 publications

References 157 publications

Lipid hijacking: A unifying theme in vector-borne diseases

Lipid hijacking: A unifying theme in vector-borne diseases

The Role of Lipoproteins in Mycoplasma-Mediated Immunomodulation

Deciphering the role of Leptospira surface protein LigA in modulating the host innate immune response

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