Unraveling the role of natural killer cells in leishmaniasis

Alizadeh, Zahra; Omidnia, Pooya; Altalbawy, Farag M. A.; Gabr, Gamal A; Obaid, Rasha Fadhel; Rostami, Narges; Aslani, Saeed; Heidari, Aliehsan; Mohammadi, Hamed

doi:10.1016/j.intimp.2022.109596

Cited by 3 publications

(1 citation statement)

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“…However, ongoing research aims to elucidate the precise roles and mechanisms of NK cells in parasitic infections. Recent data on the interaction between parasitic organisms and NK cells, such as the study by Alizadeh et al, revealed the effect of Leishmania LPG on the NK cell population 38 . They found that Leishmania LPG can limit NK cell activation by inhibiting IL‐12 synthesis in macrophages and that GP63 directly binds to NK cells and modulates their phenotype.…”

Section: Discussionmentioning

confidence: 99%

Toxoplasma gondii suppress human cord blood cell differentiation to the NK cell population

Mahmoudzadeh,

Dizaji Asl,

Nozad Charoudeh

et al. 2024

Immunity Inflam & Disease

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BackgroundToxoplasma gondii is an obligate intracellular protozoan parasite that can invade all mammalian cells. It is well established that natural killer (NK) cells have critical protective roles in innate immunity during infections by intracellular pathogens. In the current study, we conducted an in vitro experiment to evaluate NK cell differentiation and activation from human umbilical cord blood mononuclear cells (UCB‐MNCs) after infection with T. gondii tachyzoites.MethodsUCB‐MNCs were infected by fresh tachyzoites of type I (RH) or type II (PTG) strains of T. gondii pre‐expanded in mesenchymal stem cells for 2 weeks in a medium enriched with stem cell factor, Flt3, IL‐2, and IL‐15. Flow cytometry analysis and western blot analysis were performed to measure the CD57+, CD56+, and Granzyme A (GZMA).ResultsData revealed that incubation of UCB‐MNCs with NK cell differentiation medium increased the CD57+, CD56+, and GZMA. UCB‐MNCs cocultured with PTG tachyzoites showed a significant reduction of CD56+ and GZMA, but nonsignificant changes, in the levels of CD56+ compared to the control UCB‐MNCs (p > .05). Noteworthy, 2‐week culture of UCB‐MNCs with type I (RH) tachyzoites significantly suppressed CD57+, CD56+, and GZMA, showing reduction of NK cell differentiation from cord blood cells.ConclusionOur findings suggest that virulent T. gondii tachyzoites with cytopathic effects inhibit NK cell activation and eliminate innate immune responses during infection, and consequently enable the parasite to continue its survival in the host body.

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Section: Discussionmentioning

confidence: 99%

Toxoplasma gondii suppress human cord blood cell differentiation to the NK cell population

Mahmoudzadeh,

Dizaji Asl,

Nozad Charoudeh

et al. 2024

Immunity Inflam & Disease

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The role of natural anti-parasitic guided development of synthetic drugs for leishmaniasis

Pal¹,

Teli²,

Matada³

2023

European Journal of Medicinal Chemistry

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Immune response to viscerotropic Leishmania: a comprehensive review

Lodi,

Voarino,

Stocco

et al. 2024

Front. Immunol.

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L. donovani and L. infantum infections are associated with a broad clinical spectrum, ranging from asymptomatic cases to visceral leishmaniasis (VL) with high mortality rates. Clinical manifestations such as post-kala-azar dermal leishmaniasis (PKDL) and visceral leishmaniasis-associated hemophagocytic lymphohistiocytosis-mimic (VL-associated HLH-mimic) further contribute to the diversity of clinical manifestations. These clinical variations are intricately influenced by the complex interplay between the host’s immune response and the parasite’s escape mechanisms. This narrative review aims to elucidate the underlying immunological mechanisms associated with each clinical manifestation, drawing from published literature within the last 5 years. Specific attention is directed toward viscerotropic Leishmania sinfection in patients with inborn errors of immunity and acquired immunodeficiencies. In VL, parasites exploit various immune evasion mechanisms, including immune checkpoints, leading to a predominantly anti-inflammatory environment that favors parasite survival. Conversely, nearly 70% of individuals are capable of mounting an effective pro-inflammatory immune response, forming granulomas that contain the parasites. Despite this, some patients may experience reactivation of the disease upon immunosuppression, challenging current understandings of parasite eradication. Individuals living with HIV and those with inborn errors of immunity present a more severe course of infection, often with higher relapse rates. Therefore, it is crucial to exclude both primary and acquired immune deficiencies in patients presenting disease relapse and VL-associated HLH-mimic. The distinction between VL and HLH can be challenging due to clinical similarities, suggesting that the nosological entity known as VL-associated HLH may represent a severe presentation of symptomatic VL and it should be considered more accurate referring to this condition as VL-associated HLH-mimic. Consequently, excluding VL in patients presenting with HLH is essential, as appropriate antimicrobial therapy can reverse immune dysregulation. A comprehensive understanding of the immune-host interaction underlying Leishmania infection is crucial for formulating effective treatment and preventive strategies to mitigate the disease burden.

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Unraveling the role of natural killer cells in leishmaniasis

Cited by 3 publications

References 136 publications

Toxoplasma gondii suppress human cord blood cell differentiation to the NK cell population

Toxoplasma gondii suppress human cord blood cell differentiation to the NK cell population

The role of natural anti-parasitic guided development of synthetic drugs for leishmaniasis

Immune response to viscerotropic Leishmania: a comprehensive review

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