Down‐Regulation of Th1 Type of Response in Early Human American Cutaneous Leishmaniasis

Rocha, Paulo Novis; Almeida, Roque Pacheco de; Bacellar, Olı́via; Jesus, Amélia Ribeiro de; Filho, Dalmo Correia; Filho, Álvaro Cruz; Barral, Aldina; Coffman, Robert L.; Carvalho, Edgar M.

doi:10.1086/315071

Cited by 67 publications

(63 citation statements)

References 15 publications

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“…Most individuals in this trial presented ulcers with less than four weeks which could have contributed to the poor outcome observed (ROCHA et al, 1999).…”

Section: Resultsmentioning

confidence: 96%

Failure of both azithromycin and antimony to treat cutaneous leishmaniasis in Manaus, AM, Brazil

Teixeira

Paes

Guerra

et al. 2008

Rev. Inst. Med. trop. S. Paulo

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SUMMARYA non-randomized controlled clinical trial was carried out in order to evaluate both azithromycin and antimony efficacy in cutaneous leishmaniasis in Manaus, AM, Brazil. Forty nine patients from both genders, aged 14 to 70, with cutaneous ulcers for less than three months and a positive imprint for Leishmania spp. amastigotes were recruited into two groups. Group I (26 patients) received a daily-single oral dose of 500 mg of azithromycin for 20 days and Group II (23 patients) received a daily-single intramuscular dose of 20 mg/kg of meglumine antimony, also for 20 days. Azithromycin cured three of 24 (12.5%) patients on days 60, 90 and 120 respectively whereas therapeutic failure was considered in 21 of 24 (87.5%) cases. In group II, antimony cured eight of 19 (42.1%) cases as follows: three on day 30, one each on day 60 and day 90, and three on day 120. Therapeutic failure occurred in 11 of 19 (57.9%) individuals. The efficacy of antimony for leishmaniasis was better than azithromycin but analysis for the intention-to-treat response rate did not show statistical difference between them. Although azithromycin was better tolerated, it showed a very low efficacy to treat cutaneous leishmaniasis in Manaus.

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“…Most individuals in this trial presented ulcers with less than four weeks which could have contributed to the poor outcome observed (ROCHA et al, 1999).…”

Section: Resultsmentioning

confidence: 96%

Failure of both azithromycin and antimony to treat cutaneous leishmaniasis in Manaus, AM, Brazil

Teixeira

Paes

Guerra

et al. 2008

Rev. Inst. Med. trop. S. Paulo

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“…8,[23][24][25] During the early stages of the infection, before the appearance of an ulcer, there is a down modulation of IFNγ mediated by IL-10. 26 There is also evidence that IL-10 plays a major role in the pathogenesis of the disease. 27,28 The IL-10 is the most important regulatory cytokine in leishmaniasis responsible for downregulating the proinflammatory effects of IFNγ and TNF.…”

Section: Discussionmentioning

confidence: 99%

Age Modifies the Immunologic Response and Clinical Presentation of American Tegumentary Leishmaniasis

Carvalho¹,

Amorim²,

Barbosa³

et al. 2015

The American Society of Tropical Medicine and Hygiene

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Abstract. Leishmania (Viannia) braziliensis is the main causal agent of American tegumentary leishmaniasis (ATL) that may present as cutaneous, mucosal, or disseminated cutaneous leishmaniasis. The disease is highly prevalent in young males and there is a lack of studies of ATL in the elderly. Herein, we compared clinical manifestations, immunologic response, and response to antimony therapy between patients 60 years of age (N = 58) and patients who were 21-30 years of age (N = 187). The study was performed in Corte de Pedra, Bahia, Brazil, a well-known area of L. braziliensis transmission. Cytokine production by cultured peripheral blood mononuclear cells stimulated with soluble Leishmania antigen was performed. Elderly subjects more frequently had a previous history of cutaneous leishmaniasis, large lesions, or mucosal leishmaniasis, and they were less likely to have lymphadenopathy. There was no difference regarding gender and response to therapy. Peripheral blood mononuclear cells from elderly subjects produced a similar amount of tumor necrosis factor than young patients but they produced less interferon-gamma and more interleukin-10 than young subjects. We concluded that elderly patients with cutaneous leishmaniasis should be searched for mucosal or disseminated leishmaniasis. The decreased interferon-gamma production and increase in interleukin-10 observed in elderly patients may contribute to parasite persistence and L. braziliensis infection dissemination.

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“…However, the establishment of cellular mediated immune (CMI) responses, especially regulation of cytokine network involved in anti-leishmanial immunity, is likely to be associated with clinical outcome (Coutinho et al 1996, Rocha et al 1999, Toledo et al 2001). According to our results, the profiles of these CMI responses detected in subjects resistant to or recovered from leishmaniasis may provide a better understanding of the long-lived immune protection to the disease.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, IL10/IFN-γ ratio was directly related to the ability to control the infection, being higher among asymptomatics, who are considered resistant to the parasite. Although IL-10 can favor the progression of the disease in the early phase of leishmaniasis, depending on the counter balance exerted by IFN-γ, cure can be achieved due to its effector functions on parasitized macrophages (Rocha et al 1999, Bosque et al 2000. Moreover, our results strengthen the idea that the intrinsic ability to produce IL-10 in response to Leishmania infection can be a key factor in avoiding a possible harmful effect of IFN-γ, exerting an important function on regulating inflammatory responses necessary for infection control (Rocha et al 1999, Belkaid et al 2001, Gomes-Silva et al 2007.…”

Section: Discussionmentioning

confidence: 99%

T-cell responses associated with resistance to Leishmania infection in individuals from endemic areas for Leishmania (Viannia) braziliensis

Bittar

Nogueira

Vieira-Gonçalves

et al. 2007

Mem. Inst. Oswaldo Cruz

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Subclinical or asymptomatic infection is documented in individuals living in endemic areas for leishmaniasis suggesting that the development of an appropriate immune response can control parasite replication and maintain tissue integrity. A low morbidity indicates that intrinsic factors could favor resistance to Leishmania infection. Herein, leishmanial T-cell responses induced in subjects with low susceptibility to leishmaniasis as asymptomatic subjects were compared to those observed in cured cutaneous leishmaniasis (CCL) patients, who controlled the disease after antimonial therapy. All of them have shown maintenance of specific long-term immune responses characterized by expansion of higher proportions of CD4 + as compared to CD8 + Leishmania reactive T-lymphocytes. Asymptomatic subjects had lower indexes of in vitro Leishmania induced lymphoproliferative responses and interferon-gamma (IFN-γ) production in comparison to CCL patients. On the other hand, interleukin (IL-10) production was much higher in asymptomatics than in CCL, while no differences in IL-5 levels were found. In conclusion, long lived T-cell responses achieved by asymptomatic individuals differed from those who had developed symptomatic leishmaniasis in terms of intensity of lymphocyte activation (proliferation or IFN-γ) and regulatory mechanisms (IL-10). The absence of the disease in asymptomatics could be explained by their intrinsic ability to create a balance between immunoregulatory (IL-10) and effector cytokines (IFN-γ), leading to parasite destruction without producing skin tissue damage. The establishment of profiles of cell-mediated immune responses associated with resistance against Leishmania infection is likely to make new inroads into understanding the long-lived immune protection against the disease.Key words: asymptomatic infection -Leishmania (Viannia) braziliensis -cured leishmaniasis -cytokines -T-cell subsetslong term immunity (Grimaldi Jr & MacMahon-Pratt 1991). The spectrum of the clinical presentation ranges from self-healing or benign cutaneous lesions to more severe forms, such as disseminated lesions or mucosal involvement (Da-Cruz & Pirmez 2005).Studies conducted in mice and humans have unequivocally shown that a major T-cell driven component underlies the establishment of acquired immunity and protection against re-infection ( Coutinho et al. 1996, Louis et al. 1998, Bosque et al. 2000. Cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factoralpha (TNF-α) activate macrophages for killing parasites, while interleukin (IL)-4, IL-5, IL-10, and transforming grow factor-beta (TGF-β) favor intracellular parasite growth (Louis et al. 1998. In addition, IL-10 production by CD4 + CD25 + T-cells is required for maintenance of Leishmania after cure, which in turn preserves an adaptive immunity to L. (Leishmania) major (Belkaid et al. 2002).The majority of ATL patients develop cutaneous leishmaniasis (CL) (Oliveira-Neto et al. 2000), but occurrence of subclinical or asymptomatic infection strongly suggests that po...

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Down‐Regulation of Th1 Type of Response in Early Human American Cutaneous Leishmaniasis

Cited by 67 publications

References 15 publications

Failure of both azithromycin and antimony to treat cutaneous leishmaniasis in Manaus, AM, Brazil

Failure of both azithromycin and antimony to treat cutaneous leishmaniasis in Manaus, AM, Brazil

Age Modifies the Immunologic Response and Clinical Presentation of American Tegumentary Leishmaniasis

T-cell responses associated with resistance to Leishmania infection in individuals from endemic areas for Leishmania (Viannia) braziliensis

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