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Innate immune responses in Lyme borreliosis: Enhanced tumour necrosis factor-a and interleukin-12 in asymptomatic individuals in response to live spirochetes
Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery.
Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics.
Bergström, S., Department of Microbiology, University of Umeå, Umeå, Sweden.
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2005 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 141, no 1, 89-98 p.Article in journal (Refereed) Published
Abstract [en]

Innate immunity is important for early defence against borrelia spirochetes and should play a role in the clinical outcome of the infection. In order to study early cytokine responses, in vitro differentiated dendritic cells (DCs) and whole blood cells from 21 patients with different clinical outcomes of Lyme neuroborreliosis were stimulated with live borrelia spirochetes. The borrelia-induced secretion of interleukin (IL)-4, IL-10, IL-12p70, Interferon (INF)-? and tumour necrosis factor (TNF)-a in DCs and IL-1ß, IL-6, IL-8, IL-10, IL-12p70, TNF-a, regulated upon activation normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1a, MIP-1ß and eotaxin in whole blood cells was measured by enzyme-linked immunospot (ELISPOT) and multiplex arrays, respectively. We found increased numbers of TNF-a-secreting DCs (P = 0.018) in asymptomatic seropositive individuals compared to patients with subacute neuroborreliosis and seronegative controls. Asymptomatic individuals were also found to have elevated levels of IL-12p70 (P = 0.031) in whole blood cell supernatants compared to seronegative controls. These results are in line with previous experiments using cells of the adaptive immune response, indicating that strong T helper type 1 (Th1) proinflammatory responses might be associated with a successful resolution of Lyme disease. © 2005 British Society for Immunology.

Place, publisher, year, edition, pages
2005. Vol. 141, no 1, 89-98 p.
Keyword [en]
Borrelia, Clinical outcome, Dendritic cell, IL-12p70, TNF-a
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-50469DOI: 10.1111/j.1365-2249.2005.02820.xOAI: diva2:271365
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2013-11-07
In thesis
1. Clinical and Immunological Aspects of Lyme borreliosis
Open this publication in new window or tab >>Clinical and Immunological Aspects of Lyme borreliosis
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Lyme borreliosis (LB) is a tick-borne infection caused by spirochetes of the Borrelia (B.) burgdorferi sensu lato complex. The infection is associated with several clinical features, of which erythema migrans (EM) and neuroborreliosis (NB) are the most common in Europe. The prognosis after antibiotic therapy is generally good. However, some patients may have residual symptoms post-treatment. The cause of the delayed convalescence is unclear. There are several factors that may affect the clinical outcome of LB, for example, the early interaction between the host’s immune response and B. burgdorferi, the spirochete genotype, antibiotic therapy, as well as the host’s vulnerability.

This thesis aimed to explore the type of early immune response that is generated to B. burgdorferi and its importance for the clinical outcome of LB, and to study the condition of persistent symptoms post-NB from clinical, immunological and diagnostic perspectives. In total, 125 adult patients with different clinical features and outcomes of LB and 23 healthy controls were included.

In a prospective follow-up study of EM, we confirmed that the prognosis of EM is good after antibiotic therapy, and that B. afzelii is the most common B. burgdorferi genotype associated with EM in the Nordic countries. Seven patients (8%) reported persistent symptoms more than six months post-treatment. These patients had also a decreased early expression of inflammatory, Th1-type cytokines in the EM lesions, suggesting an importance of early, local Th1-type immunity to B. burgdorferi for a successful clinical outcome of LB. No correlation between clinical characteristics, allergic predisposition, B. burgdorferi genotype or serology and the development of symptoms post-treatment was found.

Asymptomatic B. burgdorferi-seropositive individuals are interesting from clinical and immunological points of view, since they apparently have encountered B. burgdorferi without developing symptoms of LB. In this thesis, asymptomatic individuals were shown to display an enhanced innate inflammatory immune response to live B. garinii spirochetes, induced by dendritic cells and whole blood cells, in comparison with patients with a history of subacute NB and healthy controls. Whether this is the optimal immune response to B. burgdorferi remains to be determined.

A randomized, placebo-controlled cross-over study showed that three weeks of doxycycline therapy did not significantly improve objective neurological signs, subjective symptoms or quality of life in NB patients with persistent symptoms post-treatment. Nor could any doxycycline-mediated effects on systemic cytokine responses be demonstrated.

Brain magnetic resonance imaging (MRI) findings in NB patients with persistent symptoms post-treatment were shown to be nonspecific and to correlate with age, but not with the duration of symptoms.

In conclusion, this thesis shows that there is an association between the early immune response to B. burgdorferi sensu lato and the clinical outcome of LB. The cause of prolonged convalescence post-treatment remains unknown and needs further investigation. However, repeated treatment with doxycycline does not lead to improvement of the persistent symptoms; nor does brain MRI facilitate diagnosis of, or provide an explanation for the post-treatment symptoms.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2011. 134 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1225
National Category
Medical and Health Sciences
urn:nbn:se:liu:diva-68745 (URN)978-91-7393-237-0 (ISBN)
Public defence
2011-05-06, Elsa Brändströms sal, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
Available from: 2011-06-01 Created: 2011-06-01 Last updated: 2013-08-29Bibliographically approved

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Sjöwall, JohannaCarlsson, AndersVaarala, OutiErnerudh, JanForsberg, PiaEkerfelt, Christina
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Clinical ImmunologyFaculty of Health SciencesSurgeryPediatricsDepartment of Clinical Immunology and Transfusion MedicineInfectious DiseasesDepartment of Infectious Diseases in Östergötland
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