Higher mRNA levels of chemokines and cytokines associated with macrophage activation in erythema migrans skin lesions in patients from the United States than in patients from Austria with Lyme borreliosis.
BACKGROUND
Erythema migrans (EM) is caused primarily by Borrelia afzelii in Europe and solely by Borrelia burgdorferi in the United States. B. burgdorferi infection in the United States has previously been associated with faster expansion of EM lesions and with more associated symptoms, compared with B. afzelii infection in Europe. However, reasons for these differences are not yet known.


METHODS
We determined the Borrelia species infecting 67 US or Austrian patients with EM. The clinical pictures and chemokine and cytokine mRNA levels in lesional skin were then compared in the 19 B. burgdorferi-infected US patients and the 37 B. afzelii-infected Austrian patients, the 2 largest groups.


RESULTS
The 19 B. burgdorferi-infected US patients had faster-expanding EM lesions and a median of 4 associated signs and symptoms, whereas the 37 B. afzelii-infected Austrian patients had slower-expanding lesions and usually did not experience associated symptoms. Compared with the EM lesions of B. afzelii-infected Austrian patients, those of B. burgdorferi-infected US patients had significantly higher mRNA levels of chemokines associated with activation of macrophages, including chemoattractants for neutrophils (CXCL1), macrophages (CCL3 and CCL4), and T helper 1 cells (CXCL9, CXCL10, and CXCL11). In addition, compared with the EM lesions of Austrian patients, the EM lesions of US patients tended to have higher mRNA levels of the macrophage-associated proinflammatory cytokines interleukin 1beta and tumor necrosis factor alpha, and they had significantly higher mRNA expression of the antiinflammatory cytokines interleukin 10 and transforming growth factor beta.


CONCLUSIONS
The EM lesions of B. burgdorferi-infected US patients expanded faster, were associated with more symptoms, and had higher mRNA levels of macrophage-associated chemokines and cytokines than did the EM lesions of B. afzelii-infected Austrian patients.
Jones
Kathryn L
KL
Division of Rheumatology, Allergy, and Immunology, Center for Immunology and Inflammatory Diseases, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. kljones@partners.org
Muellegger
Robert R
RR
Means
Terry K
TK
Lee
Marshall
M
Glickstein
Lisa J
LJ
Damle
Nitin
N
Sikand
Vijay K
VK
Luster
Andrew D
AD
Steere
Allen C
AC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001317:Austria; D001898:Borrelia / Q000276:immunology / Q000302:isolation & purification*; D018925:Chemokines / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D015787:Erythema Chronicum Migrans / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D005260:Female; D006801:Humans; D008193:Lyme Disease / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D008262:Macrophage Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D012867:Skin / Q000382:microbiology; D014481:United States
D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger