2005: immune responses to spirochetal infection.



1: Clin Diagn Lab Immunol. 2005 Aug;12(8):949-58. Related Articles,
Links


Lipoprotein-dependent and -independent immune responses to spirochetal
infection.

Salazar JC, Pope CD, Moore MW, Pope J, Kiely TG, Radolf JD.

Division of Pediatric Infectious Diseases, Connecticut Children's
Medical Center, 282 Washington Street, Hartford, Connecticut 06106.
jsalaza@xxxxxxxxxxxxx

In this study, we used the epidermal suction blister technique, in
conjunction with multiparameter flow cytometry, to analyze the cellular
and cytokine responses elicited by intradermal injection of human
volunteers with synthetic analogs for spirochetal lipoproteins and
compared the responses to findings previously reported from patients
with erythema migrans (EM). Compared with peripheral blood (PB),
lipopeptides derived from the N termini of the Borrelia burgdorferi
outer surface protein C and the 17-kDa lipoprotein of Treponema
pallidum (OspC-L and 17-L, respectively) elicited infiltrates enriched
in monocytes/macrophages and dendritic cells (DCs) but also containing
substantial percentages of neutrophils and T cells. Monocytoid
(CD11c(+)) and plasmacytoid (CD11c(-)) DCs were selectively recruited
to the skin in ratios similar to those in PB, but only the former
expressed the activation/maturation surface markers CD80, CD83, and
DC-SIGN. Monocytes/macrophages and monocytoid DCs, but not plasmacytoid
DCs, displayed significant increases in surface expression of Toll-like
receptor 1 (TLR1), TLR2, and TLR4. Staining for CD45RO and CD27
revealed that lipopeptides preferentially recruited antigen-experienced
T-cell subsets; despite their lack of antigenicity, these agonists
induced marked T-cell activation, as evidenced by surface expression of
CD69, CD25, and CD71. Lipopeptides also induced significant increases
in interleukin 12 (IL-12), IL-10, gamma interferon, and most notably
IL-6 without corresponding increases in serum levels of these
cytokines. Although lipopeptides and EM lesional infiltrates shared
many similarities, differences were noted in a number of immunologic
parameters. These studies have provided in situ evidence for a
prominent "lipoprotein effect" during human infection while at the same
time helping to pinpoint aspects of the cutaneous response that are
uniquely driven by spirochetal pathogens.

PMID: 16085913 [PubMed - in process]

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