Intralesional expression of mRNA of interferon- gamma , tumor necrosis factor- alpha , interleukin-10, nitric oxide synthase, indoleamine-2,3-dioxygenase, and RANTES is a major immune effector in Mediterranean spotted fever rickettsiosis.
BACKGROUND
The mechanisms of immunity to Rickettsia conorii that have been elucidated in mouse models have not been evaluated in human tissues.


METHODS
In this study, quantitative real-time polymerase chain reaction was used to determine the levels of expression of inflammatory and immune mediators in skin-biopsy samples collected from 23 untreated patients with Mediterranean spotted fever (MSF).


RESULTS
In all 23 patients, the levels of intralesional expression of mRNA of tumor necrosis factor (TNF)- alpha , interferon (IFN)- gamma , interleukin (IL)-10, RANTES, and indoleamine-2,3-dioxygenase (IDO), an enzyme involved in limiting rickettsial growth by tryptophan degradation, were higher than those in control subjects; 6 of the 23 patients had high levels of inducible nitric oxide synthase (iNOS), a source of microbicidal nitric oxide. Positive correlations between TNF- alpha , IFN- gamma , iNOS, IDO, and mild/moderate MSF suggest that type 1 polarization plays a protective role. Significantly higher levels of intralesional expression of IL-10 mRNA were inversely correlated with levels of intralesional expression of IFN- gamma mRNA and TNF- alpha mRNA. The mRNA-expression level of the chemokine RANTES was significantly higher in patients with severe MSF.


CONCLUSIONS
Mild/moderate MSF is associated with a strong and balanced intralesional proinflammatory and anti-inflammatory response, with a dominant type 1 immunity, whereas severe MSF is associated with increased expression of chemokine mRNA. Whether these factors are simply correlates of mild and severe MSF or contribute to antirickettsial immunity and pathogenesis remains to be determined.
Centro de Estudos de Vectores e Doencas Infecciosas, Instituto Nacional de Saude Dr Ricardo Jorge, Edificio LEMES, Lisboa, Portugal.
Rita
R
de Sousa
Nahed
N
Ismail
Sónia Dória
SD
Nobrega
Ana
A
França
Mário
M
Amaro
Margarida
M
Anes
José
J
Poças
Ricardo
R
Coelho
Jorge
J
Torgal
Fátima
F
Bacellar
David H
DH
Walker
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001907:Boutonneuse Fever / Q000235:genetics* / Q000276:immunology*; D018946:Chemokine CCL5 / Q000235:genetics* / Q000276:immunology; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics* / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology
D018946:Chemokine CCL5; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase