Intralesional expression of mRNA of interferon-γ, tumor necrosis factor-α, interleukin-10, nitric oxide synthase, indoleamine-2,3- dioxygenase, and RANTES is a major immune effector in Mediterranean spotted fever rickettsiosis

Rita De Sousa, Nahed Ismail, Sónia Dória Nobrega, Ana França, Mário Amaro, Margarida Anes, José Poças, Ricardo Coelho, Jorge Torgal, Fátima Bacellar, David Walker

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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)-α, interferon (IFN)-γ, 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-α, IFN-γ, 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-γ mRNA and TNF-α mRNA. The mRNA-expression level of the chemokine RANTES was significantly higher in patients with severe MSF. Conclusion. 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.

Original languageEnglish (US)
Pages (from-to)770-781
Number of pages12
JournalJournal of Infectious Diseases
Volume196
Issue number5
DOIs
StatePublished - Sep 1 2007

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Boutonneuse Fever
Indoleamine-Pyrrole 2,3,-Dioxygenase
Chemokine CCL5
Nitric Oxide Synthase
Interleukin-10
Interferons
Tumor Necrosis Factor-alpha
Messenger RNA
Immunity
Nitric Oxide Synthase Type II
Chemokines
Rickettsia conorii
Tryptophan
Real-Time Polymerase Chain Reaction
Nitric Oxide
Anti-Inflammatory Agents
Biopsy
Skin
Enzymes
Growth

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Intralesional expression of mRNA of interferon-γ, tumor necrosis factor-α, interleukin-10, nitric oxide synthase, indoleamine-2,3- dioxygenase, and RANTES is a major immune effector in Mediterranean spotted fever rickettsiosis. / De Sousa, Rita; Ismail, Nahed; Nobrega, Sónia Dória; França, Ana; Amaro, Mário; Anes, Margarida; Poças, José; Coelho, Ricardo; Torgal, Jorge; Bacellar, Fátima; Walker, David.

In: Journal of Infectious Diseases, Vol. 196, No. 5, 01.09.2007, p. 770-781.

Research output: Contribution to journalArticle

De Sousa, Rita ; Ismail, Nahed ; Nobrega, Sónia Dória ; França, Ana ; Amaro, Mário ; Anes, Margarida ; Poças, José ; Coelho, Ricardo ; Torgal, Jorge ; Bacellar, Fátima ; Walker, David. / Intralesional expression of mRNA of interferon-γ, tumor necrosis factor-α, interleukin-10, nitric oxide synthase, indoleamine-2,3- dioxygenase, and RANTES is a major immune effector in Mediterranean spotted fever rickettsiosis. In: Journal of Infectious Diseases. 2007 ; Vol. 196, No. 5. pp. 770-781.
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abstract = "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)-α, interferon (IFN)-γ, 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-α, IFN-γ, 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-γ mRNA and TNF-α mRNA. The mRNA-expression level of the chemokine RANTES was significantly higher in patients with severe MSF. Conclusion. 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.",
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T1 - Intralesional expression of mRNA of interferon-γ, tumor necrosis factor-α, interleukin-10, nitric oxide synthase, indoleamine-2,3- dioxygenase, and RANTES is a major immune effector in Mediterranean spotted fever rickettsiosis

AU - De Sousa, Rita

AU - Ismail, Nahed

AU - Nobrega, Sónia Dória

AU - França, Ana

AU - Amaro, Mário

AU - Anes, Margarida

AU - Poças, José

AU - Coelho, Ricardo

AU - Torgal, Jorge

AU - Bacellar, Fátima

AU - Walker, David

PY - 2007/9/1

Y1 - 2007/9/1

N2 - 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)-α, interferon (IFN)-γ, 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-α, IFN-γ, 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-γ mRNA and TNF-α mRNA. The mRNA-expression level of the chemokine RANTES was significantly higher in patients with severe MSF. Conclusion. 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.

AB - 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)-α, interferon (IFN)-γ, 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-α, IFN-γ, 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-γ mRNA and TNF-α mRNA. The mRNA-expression level of the chemokine RANTES was significantly higher in patients with severe MSF. Conclusion. 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.

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