Borrelia burgdorferi antigens in a mouse model
By Linda on Dec 7, 2009 in Infections
HLA-DR alleles determine responsiveness to Borrelia burgdorferi antigens in a
mouse model of self-perpetuating arthritis.
Iliopoulou BP, Guerau-De-Arellano M, Huber BT.
Tufts University, Boston, Massachusetts.
OBJECTIVE: Arthritis is a prominent manifestation of Lyme disease, which is
caused by infection with Borrelia burgdorferi (Bb). Chronic Lyme arthritis
persisting even after antibiotic treatment is linked to HLA-DRB1*0401 (DR4) and
related alleles. In contrast, patients whose Lyme arthritis resolves within 3
months postinfection show an increased frequency of HLA-DRB1*1101 (DR11). The
aim of this study was to analyze the underlying mechanism by which HLA-DR
alleles confer genetic susceptibility or resistance to antibiotic-refractory
Lyme arthritis.
METHODS: We generated DR11-transgenic (DR11-Tg) mice on a murine
MHCII(-/-) background and compared their immune response to Bb antigens with the
response of DR4-Tg mice after immunization with Bb outer surface protein A
(OspA) or infection with live Bb.
RESULTS: T cells from OspA-immunized and
Bb-infected DR11-Tg mice had defective production of interferon-gamma as
compared with those from DR4-Tg mice. In contrast, DR11-Tg mice developed higher
titers of anti-OspA and anti-Bb antibodies, respectively, than did DR4-Tg mice.
Consistent with this observation, we found that the Bb-infected DR11-Tg mice had
a decreased spirochetal burden as compared with the DR4-Tg mice, as measured by
quantitative polymerase chain reaction.
CONCLUSION: This study provides direct
evidence that in the presence of HLA-DR11, the immune response against Bb
antigens is directed toward a protective antibody response. In contrast, an
inflammatory Th1 response is induced in the presence of DR4. These observations
offer an explanation for the differential genetic susceptibility of DR4+ and
DR11+ individuals to the development of chronic Lyme arthritis and, eventually,
the progression to antibiotic-refractory Lyme arthritis.
http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=19950279&retmode=ref&cmd=prlinks
PMID: 19950279 [PubMed – as supplied by publisher]
