Host immune response against leishmaniasis and parasite persistence strategies: A review and assessment of recent research

Elmahallawy, Ehab Kotb; Alkhaldi, Abdulsalam A. M.; Saleh, Ayman A.

doi:10.1016/j.biopha.2021.111671

Cited by 39 publications

(43 citation statements)

References 260 publications

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“…The possibility of identifing a set of multiparametric infectious/haematochemical values (i.e., FIV, BUN and RBC, which were included in the best fitting model of infection in cats) could be used as predictive tool that could allow clinicians to consider L. infantum in their differential diagnosis. Taken into account, the resistance of a cat to Leishmania infection probably depends on genetic factors, and is not solely related to cell mediated immunity [ 20 , 82 , 83 ]. As shown, the use of direct (PCR) and indirect (WB) methods yielded discrepant results, which has allowed us to show the major advantages provided by the combined use of both methods for detection of the prevalence of infection in cats as compared to serology alone.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, the reported prevalence rate highlights the role played by cats in the transmission of disease, and this suggests cats could be either primary or secondary reservoir host for L. infantum , consistent with previous reports that revealed contraction of infection by sandflies in cats naturally infected with Leishmania [ 84 , 85 ]. The explanation for this data lies not in the difference in sensitivity of the two methods, but rather in the fact that in some species resistant to infection, like cats, the activated immune response is particularly of cell mediated rather than humoral immunity [ 78 , 82 ]. Interestingly, our present data might contribute to the hypothesis suggesting that the cat predominantly has a Th1 response, as evidenced by the high number infections (positivity to PCR) compared to the number of subjects with circulating antibodies (positive to WB), and the limited occurrence of non-specific clinical signs [ 78 , 86 ].…”

Section: Discussionmentioning

confidence: 99%

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Feline Leishmaniosis in Northwestern Italy: Current Status and Zoonotic Implications

Elmahallawy

Zanet

Poggi

et al. 2021

Veterinary Sciences

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Leishmaniasis remains one of the major neglected tropical diseases. The epidemiological profile of the disease comprises a wide range of hosts, including dogs and cats. Despite several studies about feline Leishmaniosis, the role of cats in disease epidemiology and its clinical impact is still debated. The present study raises awareness about the impact of leishmaniasis in cats from an endemic region in of Northwestern Italy (Liguria). A total number of 250 serum and 282 blood samples were collected from cats, then assessed for Leishmania infantum (L. infantum) serologically using western blot (WB) and molecularly using polymerase chain reaction (PCR). We also tested the association of Leishmania infection with some infectious agents like haemotropic Mycoplasma, Feline immunodeficiency virus (FIV) and Feline leukemia virus (FeLV) together with the hematobiochemical status of the examined animals. Interestingly, all tested animals were asymptomatic and out of 250 examined serum samples, 33 (13.20%) samples (confidence interval (CI) 95% 9.56–17.96%) were positive at WB for L. infantum, whereas of the 282 blood samples, 80 (28.36%) returned a positive PCR (CI 95% 23.43–33.89%). Furthermore, there was a statistical association between PCR positivity for L. infantum and some hematological parameters besides FIV infection as well as a direct significant correlation between Mycoplasma infection and WB positivity. Taken together, the present findings report high prevalence of L. infantum among cats, which reinforces the significance of such positive asymptomatic animals and confirms the very low humoral response in this species. In addition, the laboratory values provide evidence that infection by the parasite is linked to alteration of some hematological parameters and is correlated to some infectious agents. These data are of interest and suggest future research for accurate diagnosis of such zoonosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Feline Leishmaniosis in Northwestern Italy: Current Status and Zoonotic Implications

Elmahallawy

Zanet

Poggi

et al. 2021

Veterinary Sciences

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“…Leishmaniasis comprises a group of diseases caused by an intracellular protozoan of the genus Leishmania that are transmitted by the bite of phlebotomine sandflies. Leishmaniasis is a major public health issue, with 350 million people living at risk of developing the disease in 98 countries and with an estimated 20,000–50,000 deaths annually worldwide [ 22 , 23 ]. There are three major forms of the disease, namely, cutaneous, mucocutaneous, and visceral, all of which depend on the infective Leishmania species and the host immune response.…”

Section: Role Of Il-10-producing Nk Cells In Models Of Systemic Infectionmentioning

confidence: 99%

“…This is characterized by parasite dissemination to internal organs, such as the liver, spleen, and bone marrow, with a frequently fatal prognosis without adequate treatment. The causal species for visceral leishmaniasis are L. donovani and L. infantum/chagasi [ 22 , 23 ]. It is known that protective immune response against L. donovani infection consists of a granulomatous inflammatory response that restrains the parasite and is positively regulated by cytokines produced by both Th1 and Th2 and negatively regulated by IL-10 produced by Treg cells [ 22 , 23 , 24 , 25 , 26 ].…”

Section: Role Of Il-10-producing Nk Cells In Models Of Systemic Infectionmentioning

confidence: 99%

Role of IL-10-Producing Natural Killer Cells in the Regulatory Mechanisms of Inflammation during Systemic Infection

2021

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Natural killer (NK) cells have the dual ability to produce pro-inflammatory (IFNγ) and anti-inflammatory (IL-10) cytokines during systemic infection, which points to their crucial role both as inflammatory effectors for infection clearance and as regulators to counterbalance inflammation to limit immune-mediated damage to the host. In particular, immunosuppressive IL-10 secretion by NK cells has been described to occur in systemic, but not local, infections as a recent immunoregulatory mechanism of inflammation that may be detrimental or beneficial, depending on the timing of release, type of disease, or the infection model. Understanding the factors that drive the production of IL-10 by NK cells and their impact during dualistic inflammatory states, such as sepsis and other non-controlled inflammatory diseases, is relevant for achieving effective therapeutic advancements. In this review, the evidence regarding the immunoregulatory role of IL-10-producing NK cells in systemic infection is summarized and discussed in detail, and the potential molecular mechanisms that drive IL-10 production by NK cells are considered.

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“…The clinical outcomes of Leishmania infection depend on the early clearance of parasites by the phagocytic cells, which requires the support of T cells mediated immunity ( 45 , 46 ). The phenotypic differentiation of T cells against parasitic antigens is an important factor that eventually determines resistance or susceptibility in all forms of leishmaniasis ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

CD300a Receptor Blocking Enhances Early Clearance of Leishmania donovani From Its Mammalian Host Through Modulation of Effector Functions of Phagocytic and Antigen Experienced T Cells

et al. 2022

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The parasites of the genus Leishmania survive and proliferate in the host phagocytic cells by taking control over their microbicidal functions. The parasite also promotes differentiation of antigen-specific anti-inflammatory cytokines producing effector T cells, which eventually results in disease pathogenesis. The mechanisms that parasites employ to dominate host adaptive immunity are largely unknown. For the first time, we report that L. donovani, which causes visceral leishmaniasis in the Indian subcontinent, upregulates the expression of an immune inhibitory receptor i.e., CD300a on antigen presenting and phagocytic cells to dampen their effector functions. The blocking of CD300a signals in leishmania antigens activated macrophages and dendritic cells enhanced the production of nitric oxide, pro-inflammatory cytokines along with MHCI/II genes expression, and reduced parasitic uptake. Further, the abrogation of CD300a signals in Leishmania infected mice benefited antigen-experienced, i.e., CD4+CD44+ and CD8+CD44+ T cells to acquire more pro-inflammatory cytokines producing phenotypes and helped in the early clearance of parasites from their visceral organs. The CD300a receptor blocking also enhanced the conversion of CD4+ T effectors cells to their memory phenotypes i.e., CCR7high CD62Lhigh up to 1.6 and 1.9 fold after 14 and 21 days post-infection, respectively. These findings implicate that CD300a is an important determinant of host phagocytic cells functions and T cells differentiation against Leishmania antigens.

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Host immune response against leishmaniasis and parasite persistence strategies: A review and assessment of recent research

Cited by 39 publications

References 260 publications

Feline Leishmaniosis in Northwestern Italy: Current Status and Zoonotic Implications

Feline Leishmaniosis in Northwestern Italy: Current Status and Zoonotic Implications

Role of IL-10-Producing Natural Killer Cells in the Regulatory Mechanisms of Inflammation during Systemic Infection

CD300a Receptor Blocking Enhances Early Clearance of Leishmania donovani From Its Mammalian Host Through Modulation of Effector Functions of Phagocytic and Antigen Experienced T Cells

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