Browsing by Author "Madaan, Priyanka"

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    An Insight into Immunopathology of Leishmaniasis
    (Springer Nature, 2023-01-31T00:00:00) Chauhan, Yogesh; Nikita, Rajkumari; Madaan, Priyanka; Jain, Manju
    Leishmaniasis is a disease complex with clinical manifestations ranging from systemic visceral leishmaniasis (VL) to cutaneous leishmaniasis (CL) with skinrestricted lesions to mucocutaneous leishmaniasis (MCL) that extends to mucous membranes. These classical disease outcomes are understood as an outcome of the infecting parasite species/subspecies along with the immune correlates that define host immune status. Further each of the visceral, cutaneous and/or mucocutaneous disease forms exhibits heterogenous gradation of parasite load, extent of parasite dissemination and collateral host immunopathological damage that may result in asymptomatic, mild, moderate or severe disease phenotype. A complex network of crosstalk between immune cells, viz. neutrophils, macrophages and heterogenous T cells, with varied effector immune molecules defines the disease protective versus progressive response. Unlike a clear Th1 versus Th2 immune response in VL and CL murine models, the immune correlates in classical VL and CL human subjects exhibit a mixed response with considerable heterogeneity. A net balance of the inflammatory versus antiinflammatory immune response induced by the complement of antigen pool presented by discrete parasite species along with the immune regulation mediated by T regulatory cells drives the immunopathological outcome. Such immune heterogeneity extends to a newer disease phenomenon of atypical leishmaniasis wherein the parasite species classically known to cause VL is reported to cause cutaneous disease and vice versa. The biology of such atypical leishmaniasis cases is beginning to be explored in terms of the host immune changes apart from the differences in the parasite determinants. The chapter seeks to highlight the host immune heterogeneity that is associated with different disease outcomes in a classical setting along with atypical clinical manifestations. � The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023.
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    An Insight Into Systemic Immune Response in Leishmania donovani Mediated Atypical Cutaneous Leishmaniasis in the New Endemic State of Himachal Pradesh, India
    (Frontiers Media S.A., 2022-01-04T00:00:00) Thakur, Lovlesh; Madaan, Priyanka; Jain, Aklank; Shankar, Vinay; Negi, Ajeet; Chauhan, Shashi Bhushan; Sundar, Shyam; Singh, Om Prakash; Jain, Manju
    Leishmaniasis continues to afflict known and newer endemic sites despite global efforts towards its control and elimination. In this regard, the emergence of newer endemic sites with unusual disease formats is recognized wherein Leishmania donovani complex classically known to cause visceral disease is demonstrated to cause cutaneous manifestation. In this context, atypical cutaneous leishmaniasis (CL) cases caused by L. donovani genetic variants from the newer endemic state of Himachal Pradesh (HP) in India are beginning to be understood in terms of parasite determinants. The atypical CL manifestation further needs to be explored to define host immune correlates with a possible role in driving the unusual disease progression. In the given study, we performed comprehensive systemic-immune profiling of the atypical CL patients from the study area in HP, India, in comparison with the classical visceral leishmaniasis (VL) patients from the northeast region of India. The systemic immune response was studied using ELISA-based assessment of Th1, Th2, Th17, Treg, and Th22 specific plasma cytokine expression pattern and parasite-specific total serum IgG/IgG subclasses. The specified immune correlates are known to exhibit heterogeneous association with the different infecting parasite species, infection load, and co-lateral host immunopathology in classical CL and VL. In the atypical CL patient group, altered expression of IL-10 emerged as the key finding that could potentially fine-tune the Th1/Th17/Th22 effector cytokine axis towards a localized cutaneous manifestation. A reduced expression of IL-10 along with a high IFN-?/IL-10 ratio as a readout of effective parasite killing defined atypical cutaneous outcome. In contrast, high circulatory IL-10 levels and a depressed IFN-?/IL-10 ratio were seen in classical VL patients in line with an ineffective parasite-killing cytokine response. Overall,�the study highlights new knowledge on host immune correlates in terms of cytokine expression pattern and IgG subclasses that underline atypical disease manifestation such that L. donovani, a generally visceralizing parasite species cause skin localized cutaneous lesions. Copyright � 2022 Thakur, Madaan, Jain, Shankar, Negi, Chauhan, Sundar, Singh and Jain.