Decreased memory T-cell response and function in human immunodeficiency virus-infected patients with tegumentary leishmaniasis

Gois, Luana Leandro; Mehta, Sanjay R.; Rodrigues, Maria Zilma Andrade; Schooley, Robert T.; Badaró, Roberto; Grassi, Maria Fernanda Rios

doi:10.1590/0074-0276130174

Cited by 7 publications

(3 citation statements)

References 30 publications

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“…In this study, the patient’s disseminated clinical manifestation was probably related to the inability of the T cell-mediated immune responses to control the spread of Leishmania infection ( Da-Cruz et al, 1992 ). HIV/ Leishmania co-infected patients also present a reduction in the lymphoproliferative response to Leishmania antigens associated with the decreased quantity of both effector memory and central memory CD4 + T-cells ( Góis et al, 2014 ). A reduction in the IFN-γ and IL-13 levels and the ratio of IFN-γ/IL-10 produced in response to stimulation with soluble Leishmania antigens were also observed in individuals infected with HIV and/or cutaneous leishmaniasis ( Rodrigues et al, 2011 ).…”

Section: The Host Point Of Viewmentioning

confidence: 99%

The Binomial Parasite-Host Immunity in the Healing Process and in Reactivation of Human Tegumentary Leishmaniasis

2018

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Leishmaniasis is a vector-borne infectious disease caused by different species of protozoa from the Leishmania genus. Classically, the disease can be classified into two main clinical forms: Visceral (VL) and Tegumentary (TL) leishmaniasis. TL is a skin/mucosal granulomatous disease that manifests mainly as cutaneous localized or disseminated ulcers, papules diffusely distributed, mucosal lesions or atypical lesions. Once the etiology of the infection is confirmed, treatment can take place, and different drugs can be administered. It has already been shown that, even when the scar is clinically evident, inflammation is still present in the native tissue, and the decrease of the inflammatory process occurs slowly during the 1st years after clinical healing. The maintenance of residual parasites in the scar tissue is also well documented. Therefore, it is no longer a surprise that, under some circumstances, therapeutic failure and/or lesion reactivation occurs. All over the years, an impressive amount of data on relapses, treatment resistance and lesion reactivation after healing has been collected, and several factors have been pointed out as having a role in the process. Different factors such as Leishmania species, parasite variability, Leishmania RNA virus 1, parasite load, parasite persistence, age, nutritional status, gender, co-morbidities, co-infection, pregnancy, immunosuppression, lesion duration, number and localization of lesions, drug metabolism, irregular treatment and individual host cellular immune response were described and discussed in the present review. Unfortunately, despite this amount of information, a conclusive understanding remains under construction. In addition, multifactorial influence cannot be discarded. In this context, knowing why leishmaniasis has been difficult to treat and control can help the development of new approaches, such as drugs and immunotherapy in order to improve healing maintenance. In this sense, we would like to highlight some of the findings that may influence the course of Leishmania infection and the therapeutic response, with an emphasis on TL.

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Section: The Host Point Of Viewmentioning

confidence: 99%

The Binomial Parasite-Host Immunity in the Healing Process and in Reactivation of Human Tegumentary Leishmaniasis

2018

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“…Likewise, it is still unclear as to what impact Leishmania infection could have on the capacity of resting memory CD4 + T cells to act as a stable reservoir of latent HIV infection. What impact a spike in viral replication may have on anti-leishmanial immunity (e.g., by bystander activation of Leishmania -specific memory cells) also remains unknown ( 60 , 61 ).…”

Section: Immunopathogenesis Of Vl–hiv Coinfectionmentioning

confidence: 99%

Immunomodulatory Therapy of Visceral Leishmaniasis in Human Immunodeficiency Virus-Coinfected Patients

et al. 2018

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Patients with visceral leishmaniasis (VL)–human immunodeficiency virus (HIV) coinfection experience increased drug toxicity and treatment failure rates compared to VL patients, with more frequent VL relapse and death. In the era of VL elimination strategies, HIV coinfection is progressively becoming a key challenge, because HIV-coinfected patients respond poorly to conventional VL treatment and play an important role in parasite transmission. With limited chemotherapeutic options and a paucity of novel anti-parasitic drugs, new interventions that target host immunity may offer an effective alternative. In this review, we first summarize current views on how VL immunopathology is significantly affected by HIV coinfection. We then review current clinical and promising preclinical immunomodulatory interventions in the field of VL and discuss how these may operate in the context of a concurrent HIV infection. Caveats are formulated as these interventions may unpredictably impact the delicate balance between boosting of beneficial VL-specific responses and deleterious immune activation/hyperinflammation, activation of latent provirus or increased HIV-susceptibility of target cells. Evidence is lacking to prioritize a target molecule and a more detailed account of the immunological status induced by the coinfection as well as surrogate markers of cure and protection are still required. We do, however, argue that virologically suppressed VL patients with a recovered immune system, in whom effective antiretroviral therapy alone is not able to restore protective immunity, can be considered a relevant target group for an immunomodulatory intervention. Finally, we provide perspectives on the translation of novel theories on synergistic immune cell cross-talk into an effective treatment strategy for VL–HIV-coinfected patients.

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“…In HIV and CL co-infected patients, a similar change was not found in a study with a limited number of patients who had normal IFN-γ levels, but this change may underlie more severe cutaneous disease [31] . Patients co-infected with HIV and tegumentary leishmaniasis (the term used in South America to denote CL, MCL, or DCL) were shown to have decreased absolute numbers of effector and central memory CD4 cells with decreased function as demonstrated by response to stimulation with Leishmania antigen [32] ; however, this defect is not as profound as in HIV-VL co-infections (>350 and <200 CD4 cells/mm 3 , for tegumentary and visceral leishmaniasis, respectively) [33] . There is an increased degree of immune activation [33] .…”

Section: Immune Responses In Hiv and Leishmaniasis Co-infectionmentioning

confidence: 99%

PKDL and Other Dermal Lesions in HIV Co-infected Patients with Leishmaniasis: Review of Clinical Presentation in Relation to Immune Responses

Zijlstra¹

2014

PLoS Negl Trop Dis

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BackgroundCo-infection of leishmaniasis and HIV is increasingly reported. The clinical presentation of leishmaniasis is determined by the host immune response to the parasite; as a consequence, this presentation will be influenced by HIV-induced immunosuppression. As leishmaniasis commonly affects the skin, increasing immunosuppression changes the clinical presentation, such as in post-kala-azar dermal leishmaniasis (PKDL) and cutaneous leishmaniasis (CL); dermal lesions are also commonly reported in visceral leishmaniasis (VL) and HIV co-infection.MethodsWe reviewed the literature with regard to dermal manifestations in leishmaniasis and HIV co-infection, in three clinical syndromes, according to the primary presentation: PKDL, VL, or CL.ResultsA wide variety of descriptions of dermal leishmaniasis in HIV co-infection has been reported. Lesions are commonly described as florid, symmetrical, non-ulcerating, nodular lesions with atypical distribution and numerous parasites. Pre-existing, unrelated dermal lesions may become parasitized. Parasites lose their tropism and no longer exclusively cause VL or CL. PKDL in HIV co-infected patients is more common and more severe and is not restricted to Leishmania donovani. In VL, dermal lesions occur in up to 18% of patients and may present as (severe) localized cutaneous leishmaniasis, disseminated cutaneous leishmaniasis (DL) or diffuse cutaneous leishmaniasis (DCL); there may be an overlap with para-kala-azar dermal leishmaniasis. In CL, dissemination in the skin may occur resembling DL or DCL; subsequent spread to the viscera may follow. Mucosal lesions are commonly found in VL or CL and HIV co-infection. Classical mucocutaneous leishmaniasis is more severe. Immune reconstitution disease (IRD) is uncommon in HIV co-infected patients with leishmaniasis on antiretroviral treatment (ART).ConclusionWith increasing immunosuppression, the clinical syndromes of CL, VL, and PKDL become more severe and may overlap. These syndromes may be best described as VL with disseminated cutaneous lesions (before, during, or after VL) and disseminated cutaneous leishmaniasis with or without visceralization.

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Decreased memory T-cell response and function in human immunodeficiency virus-infected patients with tegumentary leishmaniasis

Cited by 7 publications

References 30 publications

The Binomial Parasite-Host Immunity in the Healing Process and in Reactivation of Human Tegumentary Leishmaniasis

The Binomial Parasite-Host Immunity in the Healing Process and in Reactivation of Human Tegumentary Leishmaniasis

Immunomodulatory Therapy of Visceral Leishmaniasis in Human Immunodeficiency Virus-Coinfected Patients

PKDL and Other Dermal Lesions in HIV Co-infected Patients with Leishmaniasis: Review of Clinical Presentation in Relation to Immune Responses

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