Mucosal Leishmaniasis Patients Display an Activated Inflammatory T‐cell Phenotype Associated with a Nonbalanced Monocyte Population

Gaze, Soraya; Dutra, Walderez Ornelas; Lessa, Marcus Miranda; Lessa, Hélio A.; Guimarães, Luiz Henrique; Jesus, Amélia Ribeiro de; Carvalho, Lucas P.; Machado, Paulo Roberto Lima; Carvalho, Edgar M.; Gollob, Kenneth J.

doi:10.1111/j.1365-3083.2005.01707.x

Cited by 68 publications

(78 citation statements)

References 28 publications

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“…These findings are supported by the higher production of IFN-γ and TNF-α associated with high IL-10 levels described in IND patients, while CARD patients showed an unregulated Th1 response (Bahia-Oliveira et al 1998, Correa-Oliveira et al 1999, Ribeirao et al 2000, Abel et al 2001, Gomes et al 2005. A lack of co-regulation between inflammatory and anti-inflammatory cytokines associated with severe disease was also demonstrated in human patients with leishmaniasis (Gaze et al 2006), strengthening this hypothesis.…”

Section: Discussionsupporting

confidence: 74%

Immunological imbalance between IFN-³ and IL-10 levels in the sera of patients with the cardiac form of Chagas disease

D'avila

Guedes

Castro

et al. 2009

Mem. Inst. Oswaldo Cruz

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Section: Discussionsupporting

confidence: 74%

Immunological imbalance between IFN-³ and IL-10 levels in the sera of patients with the cardiac form of Chagas disease

D'avila

Guedes

Castro

et al. 2009

Mem. Inst. Oswaldo Cruz

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“…Besides inflammatory cytokines, IL-10 is also detected in ATL lesions [28,29]. A balance between TNF/IFNγ and IL-10 seems to be important to control the infection and the inflammatory process [30,31]. Because these cytokines are related to the production and biological function of IL-32 we hypothesized that IL-32 can be induced during Leishmania infection and to contribute to the pathogenesis of the disease.…”

Section: Introductionmentioning

confidence: 99%

Interleukin 32γ (IL-32γ) is highly expressed in cutaneous and mucosal lesions of American Tegumentary Leishmaniasis patients: association with tumor necrosis factor (TNF) and IL-10

et al. 2014

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BackgroundThe interleukin 32 (IL-32) is a proinflammatory cytokine produced by immune and non-immune cells. It can be induced during bacterial and viral infections, but its production was never investigated in protozoan infections. American Tegumentary Leishmaniasis (ATL) is caused by Leishmania protozoan leading to cutaneous, nasal or oral lesions. The aim of this study was to evaluate the expression of IL-32 in cutaneous and mucosal lesions as well as in peripheral blood mononuclear cells (PBMC) exposed to Leishmania (Viannia) braziliensis.MethodsIL-32, tumour necrosis factor (TNF) and IL-10 protein expression was evaluated by immunohistochemistry in cutaneous, mucosal lesions and compared to healthy specimens. The isoforms of IL-32α, β, δ, γ mRNA, TNF mRNA and IL-10 mRNA were assessed by qPCR in tissue biopsies of lesions and healthy skin and mucosa. In addition, PBMC from healthy donors were cultured with amastigotes of L. (V.) braziliensis. In lesions, the parasite subgenus was identified by PCR-RFLP.ResultsWe showed that the mRNA expression of IL-32, in particular IL-32γ was similarly up-regulated in lesions of cutaneous (CL) or mucosal (ML) leishmaniasis patients. IL-32 protein was produced by epithelial, endothelial, mononuclear cells and giant cells. The IL-32 protein expression was associated with TNF in ML but not in CL. IL-32 was not associated with IL-10 in both CL and ML. Expression of TNF mRNA was higher in ML than in CL lesions, however levels of IL-10 mRNA were similar in both clinical forms. In all lesions in which the parasite was detected, L. (Viannia) subgenus was identified. Interestingly, L. (V.) braziliensis induced only IL-32γ mRNA expression in PBMC from healthy individuals.ConclusionsThese data suggest that IL-32 plays a major role in the inflammatory process caused by L. (Viannia) sp or that IL-32 is crucial for controlling the L. (Viannia) sp infection.

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“…This is especially true for parasitic infections. Interestingly, regulation of the adaptive immune response is essential not only for controlling parasite replication but also for minimizing immune-mediated pathology (2,7,15). It has been suggested that parasites can induce production of cytokines that decrease the expression of molecules critical for T-cell stimulation, such as major histocompatibility complex (MHC) class II and costimulatory molecules, possibly as a strategy for survival in the host (38).…”

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confidence: 99%

Trypanosoma cruziInfection Induces Differential Modulation of Costimulatory Molecules and Cytokines by Monocytes and T Cells from Patients with Indeterminate and Cardiac Chagas' Disease

et al. 2007

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Interactions between macrophages and lymphocytes through costimulatory molecules and cytokines are essential for mounting an efficient immune response and controlling its pathogenic potential. Here we demonstrate the immunomodulatory capacity of Trypanosoma cruzi, the causative agent of Chagas' disease, through its ability to induce differential expression of costimulatory molecules and cytokines by monocytes and T cells. Costimulatory molecule and cytokine modulation was evaluated using cells from noninfected individuals and from patients with the asymptomatic indeterminate form and those with the severe cardiac clinical form of Chagas' disease. Our results show that while exposure of monocytes to live T. cruzi leads to an increase in the frequency of CD80 ؉ monocytes in all groups, it decreases both the frequency and intensity of CD86 expression by monocytes from patients with the cardiac form but not from those with the indeterminate form. Conversely, exposure of lymphocytes to monocytes infected with T. cruzi increased the surface expression of cytotoxic-Tlymphocyte-associated antigen 4 (CTLA-4) by T cells from indeterminate but not from cardiac patients, compared to that from control patients. These data suggest that T. cruzi induces a potentially down-regulatory environment in indeterminate subjects, which is associated with higher CD80 and CTLA-4 expression. To test the functional importance of this modulation, we evaluated the expression of cytokines after in vitro infection. Although exposure of lymphocytes to parasite-infected monocytes induced high expression of inflammatory and anti-inflammatory cytokines by T cells in all groups, indeterminate patients displayed a higher ratio of monocytes expressing interleukin 10 than tumor necrosis factor alpha following infection than did controls. These data show the ability of T. cruzi to actively change the expression of costimulatory molecules and cytokines, suggesting molecular mechanisms for the differential clinical evolution of human Chagas' disease.

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Mucosal Leishmaniasis Patients Display an Activated Inflammatory T‐cell Phenotype Associated with a Nonbalanced Monocyte Population

Cited by 68 publications

References 28 publications

Immunological imbalance between IFN-³ and IL-10 levels in the sera of patients with the cardiac form of Chagas disease

Immunological imbalance between IFN-³ and IL-10 levels in the sera of patients with the cardiac form of Chagas disease

Interleukin 32γ (IL-32γ) is highly expressed in cutaneous and mucosal lesions of American Tegumentary Leishmaniasis patients: association with tumor necrosis factor (TNF) and IL-10

Trypanosoma cruziInfection Induces Differential Modulation of Costimulatory Molecules and Cytokines by Monocytes and T Cells from Patients with Indeterminate and Cardiac Chagas' Disease

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