Early Cytokine Release in Response to Live Borrelia burgdorferi Sensu Lato Spirochetes Is Largely Complement Independent

Sandholm, Kerstin; Henningsson, Anna J.; Säve, Susanne; Bergström, Sven; Forsberg, Pia; Jönsson, Nina; Ernerudh, Jan; Ekdahl, Kristina Nilsson

doi:10.1371/journal.pone.0108013

Cited by 8 publications

(12 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…bind human and various animal C4BP (143, 148, 149, 157, 158). A comprehensive analysis identified outer surface proteins (Osps) associated with C4BP including OspA, Vlps, variable membrane proteins (Vmps), and several unidentified Osps (159).…”

Section: Inhibition Of the Mammalian Complement System By Borrelia Anmentioning

confidence: 99%

“…An interesting hypothesis was developed regarding complement resistance and spirochete niche when a relationship was noted between binding of the complement inhibitors, C4BP and FH (157, 158, 161). Neurotropic strains (e.g., B. bavariensis, B. garinii, B. turicatae, B. duttonii , and to a lesser extent B. hermsii ) do not have to be highly resistant to complement in immunoprivileged sites, such as the central nervous system.…”

Section: Inhibition Of the Mammalian Complement System By Borrelia Anmentioning

confidence: 99%

“…Perhaps C4BP is sufficient to prevent complement activation during migration of neurotropic species from the site of inoculation to immunoprivileged sites. On the other hand, binding FH may be important for neurotropic strains to resist complement during migration and the incomplete sensitivity observed by Sandholm et al (158) may be due to in vitro culturing resulting in the population losing its ability to bind FH. It could also be that neither C4BP nor FHBPs play a role in complement-sensitive borreliae disseminating and a novel mechanism is utilized by complement-sensitive strains.…”

Section: Inhibition Of the Mammalian Complement System By Borrelia Anmentioning

confidence: 99%

See 2 more Smart Citations

Host Immune Evasion by Lyme and Relapsing Fever Borreliae: Findings to Lead Future Studies for Borrelia miyamotoi

Stone

Brissette

2017

Front. Immunol.

View full text Add to dashboard Cite

The emerging pathogen, Borrelia miyamotoi, is a relapsing fever spirochete vectored by the same species of Ixodes ticks that carry the causative agents of Lyme disease in the US, Europe, and Asia. Symptoms caused by infection with B. miyamotoi are similar to a relapsing fever infection. However, B. miyamotoi has adapted to different vectors and reservoirs, which could result in unique physiology, including immune evasion mechanisms. Lyme Borrelia utilize a combination of Ixodes-produced inhibitors and native proteins [i.e., factor H-binding proteins (FHBPs)/complement regulator-acquiring surface proteins, p43, BBK32, BGA66, BGA71, CD59-like protein] to inhibit complement, while some relapsing fever spirochetes use C4b-binding protein and likely Ornithodoros-produced inhibitors. To evade the humoral response, Borrelia utilize antigenic variation of either outer surface proteins (Osps) and the Vmp-like sequences (Vls) system (Lyme borreliae) or variable membrane proteins (Vmps, relapsing fever borreliae). B. miyamotoi possesses putative FHBPs and antigenic variation of Vmps has been demonstrated. This review summarizes and compares the common mechanisms utilized by Lyme and relapsing fever spirochetes, as well as the current state of understanding immune evasion by B. miyamotoi.

show abstract

Section: Inhibition Of the Mammalian Complement System By Borrelia Anmentioning

confidence: 99%

Section: Inhibition Of the Mammalian Complement System By Borrelia Anmentioning

confidence: 99%

Section: Inhibition Of the Mammalian Complement System By Borrelia Anmentioning

confidence: 99%

See 1 more Smart Citation

Host Immune Evasion by Lyme and Relapsing Fever Borreliae: Findings to Lead Future Studies for Borrelia miyamotoi

Stone

Brissette

2017

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…The spirochete employs a number of immune evasion strategies, which aid the establishment of a persistent infection, including antigenic variation, the production of complement inhibiting, or complement resistant proteins and the secretion of a protease, enabling its localization in Bsanctuary sites^in the extracellular matrix [201,202]. It is not surprising therefore that Bf infection stimulates the production of a range of chemokines and cytokines by macrophages including IL-8, IL-10, TNFα, IL-6, and IL-1β, leading to the generation of systemic inflammation, largely independent of the activation of the complement system [203,204]. Bf-mediated immune activation and inflammation is effected by spirochete LPS engagement with TLR2 and TLR4 [205].…”

Section: Borrelia Burgdorferimentioning

confidence: 99%

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

Morris¹,

Berk

Walder

et al. 2015

Mol Neurobiol

View full text Add to dashboard Cite

Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited, with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls. Similarly, exercise regimes either produce significant, but practically unimportant, benefit or provoke symptom exacerbation. Many such patients are afforded the exclusionary, non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms. More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure. Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed, how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased. The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients, and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles, genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.

show abstract

“…The complement system is a part of the innate immunity and provides a link to the adaptive immune system. It consists of a large number of plasma and membrane-linked proteins that work in a close network and a cascade-linked manner [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Complement activation in individuals with previous subclinical Lyme borreliosis and patients with previous Lyme neuroborreliosis

Carlsson

Sandholm

Haddish

et al. 2019

Eur J Clin Microbiol Infect Dis

Self Cite

View full text Add to dashboard Cite

Lyme borreliosis (LB) is caused by Borrelia burgdorferi and infection may lead to not only a large variety of clinical manifestations but also a subclinical outcome. The aim of the present study was to investigate if there is a constitutional difference in complement activation between individuals with previous subclinical Lyme borreliosis (SB) and patients previously diagnosed with Lyme neuroborreliosis (LNB). Lepirudin plasma for activation studies was collected from 60 SB individuals and from 22 patients pre-diagnosed with LNB. The plasma was incubated with live Borrelia spirochetes of two strains (complement sensitive B. garinii Lu59 and complement resistant B. afzelii ACA1). Complement factor C3 was measured in non-activated lepirudin plasma with immune-nephelometry and C3a and sC5b-9 generated during complement activation were measured by enzyme-linked immunosorbent assay. We found that the complement sensitive Lu59 induced higher complement activation than the complement resistant ACA1 when measuring activation products C3a and sC5b-9 in SB and LNB patients, p < 0.0001. No significant difference was found between SB and LNB patients in systemic levels of C3. Furthermore, SB individuals generated a higher activation of C3 cleavage to C3a (C3a/C3 ratio) than LNB patients after activation with ACA1, p < 0.001, but no significant differences were found in response to Lu59. In conclusion, Lu59 induced higher complement activation than ACA1 and individuals with previous SB showed increased generation of C3a compared with patients with previous LNB. In our study population, this mechanism could lead to less elimination of spirochetes in LNB patients and thereby be a factor contributing to the clinical outcome.

show abstract

Early Cytokine Release in Response to Live Borrelia burgdorferi Sensu Lato Spirochetes Is Largely Complement Independent

Cited by 8 publications

References 69 publications

Host Immune Evasion by Lyme and Relapsing Fever Borreliae: Findings to Lead Future Studies for Borrelia miyamotoi

Host Immune Evasion by Lyme and Relapsing Fever Borreliae: Findings to Lead Future Studies for Borrelia miyamotoi

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

Complement activation in individuals with previous subclinical Lyme borreliosis and patients with previous Lyme neuroborreliosis

Contact Info

Product

Resources

About