Department Of Zoology

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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.
An intraspecies Leishmania donovani hybrid from the Indian subcontinent is associated with an atypical phenotype of cutaneous disease
(Elsevier Inc., 2022-01-22T00:00:00) Lypaczewski, Patrick; Thakur, Lovlesh; Jain, Aklank; Kumari, Sandhya; Paulini, Kayla; Matlashewski, Greg; Jain, Manju
Leishmaniasis is a neglected tropical disease endemic in over 90 countries. The disease has two main pathologies; cutaneous leishmaniasis (CL) that generally self-heals, and visceral leishmaniasis (VL) that is fatal if untreated. The majority of VL cases, concentrated on the Indian subcontinent (ISC) and East Africa, are caused by Leishmania donovani. However, recent foci of CL on the ISC have been attributed as an atypical phenotype of L. donovani including a recent outbreak in Himachal Pradesh, India. Whole genome sequencing and phylogenetic analysis was undertaken to investigate the origins and genetic factors leading to this pathology atypical of L. donovani. Here we demonstrate the isolate from Himachal Pradesh is derived from a genetic hybridization between two independent L. donovani parents from the �Yeti� ISC1 divergent clade of parasites, identified in the Nepalese highlands. This reveals that intraspecies L. donovani hybrids can give rise to a novel strain associated with CL. � 2022 The Author(s)
Yin and yang of immunological memory in controlling infections: Overriding self defence mechanisms
(Taylor and Francis Ltd., 2021-04-19T00:00:00) Roy, Roshan Kumar; Yadav, Rakhi; Jain, Aklank; Tripathi, Vishwas; Jain, Manju; Singh, Sandhya; Prakash, Hridayesh
Immunological memory is critical for host immunity and decisive for individual to respond exponentially to previously encountered infection. Both T and B cell memory are known to orchestrate immunological memory with their central and effector memory arms contributing in prolonged immunity/defence mechanisms of host. While central memory helps in maintaining prolonged immunity for a particular infection, effector memory helps in keeping local/seasonal infection in control. In addition to this, generation of long-lived plasma cells is pivotal for generating neutralizing antibodies which can enhance recall and B cell memory to control re-infection. In view of this, scaling up memory response is one of the major objectives for the expected outcome of vaccination. In this line, this review deals with the significance of memory cells, molecular pathways of their development, maintenance, epigenetic regulation and negative regulation in various infections. We have also highlighted the significance of both T and B cell memory responses in the vaccination approaches against range of infections which is not fully explored so far. Highlights Pathogens induce IL-10R, PD-1, T-reg; and downregulate IL7R and IL15R for hijacking memory response IL-7, 15, Tcf-1 (Wnt5/7A), and CD28 signaling is decisive for TCM/TEM and TRM recall. Bach2 expression suppress Bim and Puma and promotes memory B cell activities VCAM1, IFN-?, and GM-CSF pathways are critical for local activation of memory cells Multi-epitope vaccines/adjuvants are potent for inducing specific memory response. � 2021 Taylor & Francis Group, LLC.

Department Of Zoology

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