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Review
. 2023 May 17:10:1096458.
doi: 10.3389/fmed.2023.1096458. eCollection 2023.

Immunotherapy and immunochemotherapy in combating visceral leishmaniasis

Ganesh Yadagiri  1   2 , Aakriti Singh  1 , Kanika Arora  1 , Shyam Lal Mudavath  1
Affiliations
Review

Immunotherapy and immunochemotherapy in combating visceral leishmaniasis

Ganesh Yadagiri et al. Front Med (Lausanne). .

Abstract

Visceral leishmaniasis (VL), a vector-borne disease, is caused by an obligate intramacrophage, kinetoplastid protozoan parasite of the genus Leishmania. Globally, VL is construed of diversity and complexity concerned with high fatality in tropics, subtropics, and Mediterranean regions with ~50,000-90,000 new cases annually. Factors such as the unavailability of licensed vaccine(s), insubstantial measures to control vectors, and unrestrained surge of drug-resistant parasites and HIV-VL co-infections lead to difficulty in VL treatment and control. Furthermore, VL treatment, which encompasses several problems including limited efficacy, emanation of drug-resistant parasites, exorbitant therapy, and exigency of hospitalization until the completion of treatment, further exacerbates disease severity. Therefore, there is an urgent need for the development of safe and efficacious therapies to control and eliminate this devastating disease. In such a scenario, biotherapy/immunotherapy against VL can become an alternative strategy with limited side effects and no or nominal chance of drug resistance. An extensive understanding of pathogenesis and immunological events that ensue during VL infection is vital for the development of immunotherapeutic strategies against VL. Immunotherapy alone or in combination with standard anti-leishmanial chemotherapeutic agents (immunochemotherapy) has shown better therapeutic outcomes in preclinical studies. This review extensively addresses VL treatment with an emphasis on immunotherapy or immunochemotherapeutic strategies to improve therapeutic outcomes as an alternative to conventional chemotherapy.

Keywords: chemotherapy; drug resistance; immunochemotherapy; immunotherapy; visceral leishmaniasis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Immune modulation in visceral leishmaniasis. Macrophages, neutrophils, natural killer (NK) cells, and dendritic cells (DCs) play an essential role by sensing parasitic first occurrence via pattern recognition receptors (PRRs) and complement receptors present on host cells. Recognition and interaction stimulate intracellular signaling pathways that lead to the occurrence of inflammatory responses and control parasite multiplication. Leishmania-infected macrophages and dendritic cells activate Th1 cell differentiation and generate inflammatory cytokines especially IL-12, IFN-γ, reactive oxygen, and nitric oxide species supporting intra-cellular parasite clearance and enhanced levels of Th2 cytokines resulting in disease progression.
Figure 2
Figure 2
Immunobiology during pathogenesis in visceral leishmaniasis: Leishmania parasite invades macrophages and activates CD4 T cells to release Th1- (IL-12, IFN-γ, and nitric oxide) and Th2 (IL-10 and TGF-β)-type cytokine responses. VL pathogenesis is mediated through the augmented expression of Th2-type cytokines, and VL clearance is arbitrated through the increased Th1 cytokine responses.
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Grants and funding

GY is thankful to the Department of Science and Technology (DST) for providing financial support. This work was supported by the SERB (DST), Government of India for funding (EEQ/2020/000563).

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