scholarly journals The Brilliance of Borrelia: Mechanisms of Host Immune Evasion by Lyme Disease-Causing Spirochetes

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 281
Author(s):  
Cassidy Anderson ◽  
Catherine A. Brissette
Keyword(s):  
Immune Response ◽  
Lyme Disease ◽  
Immune Evasion ◽  
Host Immune Response ◽  
Surface Proteins ◽  
Borrelia Burgdorferi Sensu Lato ◽  
Adaptive Responses ◽  
Tick Saliva ◽  
Vector Borne ◽  
Antimicrobial Peptide Resistance

Lyme disease (LD) has become the most common vector-borne illness in the northern hemisphere. The causative agent, Borrelia burgdorferi sensu lato, is capable of establishing a persistent infection within the host. This is despite the activation of both the innate and adaptive immune responses. B. burgdorferi utilizes several immune evasion tactics ranging from the regulation of surface proteins, tick saliva, antimicrobial peptide resistance, and the disabling of the germinal center. This review aims to cover the various methods by which B. burgdorferi evades detection and destruction by the host immune response, examining both the innate and adaptive responses. By understanding the methods employed by B. burgdorferi to evade the host immune response, we gain a deeper knowledge of B. burgdorferi pathogenesis and Lyme disease, and gain insight into how to create novel, effective treatments.

scholarly journals Vaccination against Lyme disease caused by diverse Borrelia burgdorferi.

1995 ◽  
Vol 181 (1) ◽  
pp. 215-221 ◽  
Author(s):  
E Fikrig ◽  
S R Telford ◽  
R Wallich ◽  
M Chen ◽  
Y Lobet ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Classification Systems ◽  
Surface Proteins ◽  
Borrelia Burgdorferi Sensu Lato ◽  
Natural Mode ◽  
Naturally Occurring ◽  
Vector Borne

Diversity and mutations in the genes for outer surface proteins (Osps) A and B of Borrelia burgdorferi sensu lato (B. burgdorferi), the spirochetal agent of Lyme disease, suggests that a monovalent OspA or OspB vaccine may not provide protection against antigenically variable naturally occurring B. burgdorferi. We now show that OspA or OspB immunizations protect mice from tick-borne infection with heterogeneous B. burgdorferi from different geographic regions. This result is in distinct contrast to in vitro killing analyses and in vivo protection studies using syringe injections of B. burgdorferi as the challenge inoculum. Evaluations of vaccine efficacy against Lyme disease and other vector-borne infections should use the natural mode of transmission and not be predicated on classification systems or assays that do not rely upon the vector to transmit infection.

scholarly journals Demonstration of the Genetic Stability and Temporal Expression of Select Members of the Lyme Disease Spirochete OspF Protein Family during Infection in Mice

2001 ◽  
Vol 69 (8) ◽  
pp. 4831-4838 ◽  
Author(s):  
John V. McDowell ◽  
Shian Ying Sung ◽  
Gregory Price ◽  
Richard T. Marconi
Keyword(s):  
Immune Response ◽  
Lyme Disease ◽  
Gene Family ◽  
Immune Evasion ◽  
Humoral Immune Response ◽  
Genetic Stability ◽  
Gene Families ◽  
Time Frame ◽  
Protein Family ◽  
Humoral Immune

ABSTRACT Infection with Lyme disease spirochetes can be chronic. This suggests that the spirochetes are capable of immune evasion. In a previous study we demonstrated that the ospE gene family, which is one of three gene families whose members are flanked at their 5′ end by the highly conserved upstream homology box (UHB) element, undergoes mutation and rearrangement during infection. This results in the generation of antigenically distinct variants that may contribute to immune evasion. In this study we have assessed the genetic stability of the UHB-flanked ospF gene family during infection in mice. Using postinfection clonal populations of Borrelia burgdorferi B31MI, PCR amplicons were generated for three members of the ospF gene family after a 3-month infection time frame. The amplicons were analyzed by single-nucleotide polymorphism pattern analysis and DNA sequencing. Members of the ospFgene family were found to be stable during infection, as no mutations or rearrangements were detected. An analysis of the humoral immune response to these proteins during infection revealed that the immune response to each is specific and that there is a delayed humoral immune response to some OspF protein family members. These analyses suggest that there is a temporal component to the expression of these genes during infection. In addition to a possible contribution to immune evasion, members of the OspF protein family may play specific roles at different stages of infection.

scholarly journals Genospecies Identification and Characterization of Lyme Disease Spirochetes of Genospecies Borrelia burgdorferi Sensu Lato Isolated from Rodents in Taiwan

1998 ◽  
Vol 36 (11) ◽  
pp. 3127-3132 ◽  
Author(s):  
Chien-Ming Shih ◽  
Han-Ming Chang ◽  
Show-Li Chen ◽  
Li-Lian Chao
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Pcr Primers ◽  
Sensu Stricto ◽  
Surface Proteins ◽  
Borrelia Burgdorferi Sensu Lato ◽  
Pcr Analysis ◽  
Protein Profiles ◽  
Specific Pcr ◽  
Plasmid Profiles

Lyme disease spirochetes of the genospecies Borrelia burgdorferi sensu lato were identified and characterized for the first time in Taiwan. Seven isolates, designated TWKM1 to TWKM7, were purified from the ear tissues of three species of rodents captured from seven localities of Taiwan. The immunological characteristics of these Taiwan isolates were compared with those of other genospecies of Lyme disease spirochetes by analyzing the protein profiles and reactivities with B. burgdorferi-specific monoclonal antibodies (MAbs). The genospecies of these Taiwan isolates were also identified by the similarities in their plasmid profiles and differential reactivities with genospecies-specific PCR primers. Although two distinct protein profiles were observed among the seven Taiwan isolates, the MAb reactivities against the outer surface proteins of B. burgdorferi of all of these isolates were consistent with those of B. burgdorferi sensu lato. The similarities of the plasmid profiles also confirmed the identities of these Taiwan isolates. PCR analysis indicated that all of these Taiwan isolates were genetically related to the genospecies B. burgdorferi sensu stricto. These results demonstrate the first identification of Lyme disease spirochetes in Taiwan and also highlight the increasing demand for defining the reservoirs and vector ticks of B. burgdorferi. A serosurvey for Lyme disease infection in the human population of Taiwan may also be required.

Understanding the immune responses involved in mediating protection or immunopathology during leishmaniasis

2021 ◽  
Author(s):  
Thalia Pacheco-Fernandez ◽  
Greta Volpedo ◽  
Chaitenya Verma ◽  
Abhay R. Satoskar
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Public Health Problem ◽  
Host Immune Response ◽  
Sand Fly ◽  
Leishmania Infection ◽  
Major Public Health Problem ◽  
Wide Range ◽  
Vector Borne ◽  
Leishmania Parasites

Leishmaniasis is a vector-borne Neglected Tropical Disease (NTD) transmitted by the sand fly and is a major public health problem worldwide. Infections caused by Leishmania clinically manifest as a wide range of diseases, such as cutaneous (CL), diffuse cutaneous (DCL), mucosal (MCL) and visceral leishmaniasis (VL). The host innate and adaptative immune responses play critical roles in the defense against leishmaniasis. However, Leishmania parasites also manipulate the host immune response for their survival and replication. In addition, other factors such as sand fly salivary proteins and microbiota also promote disease susceptibility and parasite spread by modulating local immune response. Thus, a complex interplay between parasite, sand fly and the host immunity governs disease severity and outcome. In this review, we discuss the host immune response during Leishmania infection and highlight the factors associated with resistance or susceptibility.

scholarly journals The Tick Salivary Protein Salp15 Inhibits the Killing of Serum-Sensitive Borrelia burgdorferi Sensu Lato Isolates

2008 ◽  
Vol 76 (7) ◽  
pp. 2888-2894 ◽  
Author(s):  
Tim J. Schuijt ◽  
Joppe W. R. Hovius ◽  
Nathalie D. van Burgel ◽  
Nandhini Ramamoorthi ◽  
Erol Fikrig ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Ixodes Scapularis ◽  
Membrane Attack Complex ◽  
Salivary Protein ◽  
Borrelia Burgdorferi Sensu Lato ◽  
Protective Effects ◽  
Tick Saliva ◽  
Specific Antibodies ◽  
Normal Human

ABSTRACT Borrelia burgdorferi, the agent of Lyme disease, is transmitted by ticks. During transmission from the tick to the host, spirochetes are delivered with tick saliva, which contains the salivary protein Salp15. Salp15 has been shown to protect spirochetes against B. burgdorferi-specific antibodies. We now show that Salp15 from both Ixodes ricinus and Ixodes scapularis protects serum-sensitive isolates of Borrelia burgdorferi sensu lato against complement-mediated killing. I. ricinus Salp15 showed strong protective effects compared to those of I. scapularis Salp15. Deposition of terminal C5b to C9 (one molecule each of C5b, C6, C7, and C8 and one or more molecules of C9) complement complexes, part of the membrane attack complex, on the surface of B. burgdorferi was inhibited in the presence of Salp15. In the presence of normal human serum, serum-sensitive Borrelia burgdorferi requires protection against complement-mediated killing, which is provided, at least in part, by the binding to the tick salivary protein Salp15.

scholarly journals LYME BORRELIOSIS IN NORTH BACKA DISTRICT

2017 ◽  
Vol 10 (2) ◽  
pp. 81-94
Author(s):  
Dragica Kovačević Berić ◽  
Tibor Molnar ◽  
Morana Miković ◽  
Sara Savić
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Average Rate ◽  
Borrelia Burgdorferi Sensu Lato ◽  
Prevalence Rates ◽  
Serological Tests ◽  
Causative Agents ◽  
Vector Borne ◽  
Epidemiological Characteristics ◽  
Moderate Climate

Lyme disease is the most common vector borne disease in regions with moderate climate. The cause of the disease is Borrelia burgdorferi sensu lato (B. burgdorferi s.l.), whereas infection is spread via bite from a tick carrying the causative agent. The objective of this work is the examination of descriptive-epidemiological characteristics of Lyme disease in North Backa region in the period from 2012 to 2016. In terms of classifi cation, Lyme dis-ease does not fall into the category of diseases that must be reported when infection occurs among animals. The average rate of incidence in humans during the observed five-year period is 7/100.000. Th e highest incidence of this disease among humans was observed in 2013 (In 12.2/100,000) with 22 reported cases, whereas the lowest incidence was in 2015 (In 5.0/100,000) with 9 reported cases. The highest rate of incidence was recorded in Bačka Topola municipality – 15.9/100.000; followed by Mali Iđoš with 7.2/100.000; while the lowest rate was recorded in Subotica being 5.0 cases per 100,000 residents. Th e presence of the disease was confi rmed in all patients via labo-ratory (serological) tests. Women were more likely to become infected, with the male-female patient ratio being 41%-59%. The disease was documented predominantly among people aged 50-69. The majority of cases were re-corded during spring and summer, in the period from May to June (71%). Among animals, the disease was documented in Subotica and Mali Iđoš municipality, with average prevalence rates among dogs and horses being 0.07%; and 1.52% respectively. Subotica municipality has the most accurate records of cases and a prevalence of 0.06% among dogs, and 1.43% among horses, while Mali Iđoš municipality has higher prevalence, being 2.99% among horses and 0.14% among dogs. The highest occurrence of Lyme disease among animals was documented in 2015, with a prevalence of 2.85% among horses. The presence of causative agents among examined ticks in Mali Iđoš municipality was 16.28% on average, predominantly in 2015 (in 21.21% of examined ticks).

scholarly journals ‘2TM proteins’: an antigenically diverse superfamily with variable functions and export pathways

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4757 ◽  
Author(s):  
Jasweer Kaur ◽  
Rachna Hora
Keyword(s):  
Immune Response ◽  
Plasmodium Falciparum ◽  
Immune Evasion ◽  
Secretory Pathway ◽  
Surface Display ◽  
Domain Architecture ◽  
Host Immune Response ◽  
Membrane Topology ◽  
Surface Topology ◽  
Variable Surface

Malaria is a disease that affects millions of people annually. An intracellular habitat and lack of protein synthesizing machinery in erythrocytes pose numerous difficulties for survival of the human pathogenPlasmodium falciparum. The parasite refurbishes the infected red blood cell (iRBC) by synthesis and export of several proteins in an attempt to suffice its metabolic needs and evade the host immune response. Immune evasion is largely mediated by surface display of highly polymorphic protein families known as variable surface antigens. These include the two trans-membrane (2TM) superfamily constituted by multicopy repetitive interspersed family (RIFINs), subtelomeric variable open reading frame (STEVORs) andPlasmodium falciparumMaurer’s cleft two trans-membrane proteins present only inP. falciparumand some simian infectingPlasmodiumspecies. Their hypervariable region flanked by 2TM domains exposed on the iRBC surface is believed to generate antigenic diversity. Though historically named “2TM superfamily,” several A-type RIFINs and some STEVORs assume one trans-membrane topology. RIFINs and STEVORs share varied functions in different parasite life cycle stages like rosetting, alteration of iRBC rigidity and immune evasion. Additionally, a member of the STEVOR family has been implicated in merozoite invasion. Differential expression of these families in laboratory strains and clinical isolates propose them to be important for host cell survival and defense. The role of RIFINs in modulation of host immune response and presence of protective antibodies against these surface exposed molecules in patient sera highlights them as attractive targets of antimalarial therapies and vaccines. 2TM proteins arePlasmodiumexport elements positive, and several of these are exported to the infected erythrocyte surface after exiting through the classical secretory pathway within parasites. Cleaved and modified proteins are trafficked after packaging in vesicles to reach Maurer’s clefts, while information regarding delivery to the iRBC surface is sparse. Expression and export timing of the RIFIN andPlasmodium falciparumerythrocyte membrane protein1 families correspond to each other. Here, we have compiled and comprehended detailed information regarding orthologues, domain architecture, surface topology, functions and trafficking of members of the “2TM superfamily.” Considering the large repertoire of proteins included in the 2TM superfamily and recent advances defining their function in malaria biology, a surge in research carried out on this important protein superfamily is likely.

scholarly journals Infection of Mice with Lyme Disease Spirochetes Constitutively Producing Outer Surface Proteins A and B

2007 ◽  
Vol 75 (6) ◽  
pp. 2786-2794 ◽  
Author(s):  
Keith O. Strother ◽  
Emir Hodzic ◽  
Stephen W. Barthold ◽  
Aravinda M. de Silva
Keyword(s):  
Immune Response ◽  
Lyme Disease ◽  
Outer Surface ◽  
Severe Disease ◽  
Protein A ◽  
Surface Protein ◽  
Surface Proteins ◽  
Mammalian Host ◽  
Outer Surface Protein A ◽  
Immunocompetent Mice

ABSTRACT Outer surface protein A (OspA) of the Lyme disease spirochete is primarily produced in the tick vector. OspA, which is a receptor for attaching spirochetes to the tick gut, is down regulated as the spirochetes leave the tick and enter the mammalian host. Although OspA is not a major antigen produced in the mammal, the protein appears to be produced under some conditions and production has been linked to more severe disease. A Lyme disease vaccine based on recombinant OspA has been approved for human use. However, the vaccine is no longer available, in part because of fears that OspA causes arthritis in people. To further understand the consequences of OspA production in the host, we created a Borrelia burgdorferi mutant that was unable to down regulate OspA. C3H/HeN mice infected with this mutant developed a specific anti-OspA immune response, and the spirochetes were unable to persist in these mice. In contrast, immunodeficient SCID mice were persistently infected with the mutant. We conclude that spirochetes producing OspA and B from the flaB promoter in immunocompetent mice stimulate an immune response that clear the bacteria without any signs of disease development in the mice.

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