The NIAID International Center for Excellence in Research (ICER) in India is a collaborative research partnership between NIAID and the Indian Ministry of Health and Family Welfare, specifically the Department of Health Research (DHR) and the Indian Council of Medical Research (ICMR).
ICER India is a team of U.S. and Indian researchers who use clinical research and field observations to drive laboratory investigations of endemic infectious diseases of particular importance in India. Located in the campus of ICMR-National Institute of Research in Tuberculosis (NIRT) in Chennai, the ICER facility has laboratory space equipped for molecular biology, biochemistry, immunology with instruments that include sequencers, flow cytometers (a FACS Cellesta and a FACS Canto), two Luminex machines including a Magpix, real-time RT-PCR, standard thermocyclers, biosafety cabinets, centrifuges, microfuges among others. This site has superb clinical research infrastructure (staff trained in good laboratory practices [GLP] and good clinical practices [GCP]), accredited investigational review boards (IRBs), networked and secured clinical trials databases, and highly evolved IT services with secure collaborative servers. The ICER has ongoing studies using electronic databases including DataFax and RedCap and pioneered the use of electronic case report forms (CRFs) for international NIAID studies. It is equipped with secure collaborative servers that enable secure transfer of large-scale data between India and the United States.
ICER India has multiple clinical field sites as well as hospital and health care clinical sites for patient recruitment in and around Chennai, in addition to numerous research collaborations partnering with scientists and institutions within India and internationally. Through these research partnerships, individual and institution research capacities are developed, and local research capacity is strengthened to tackle endemic, emerging, and re-emerging infections.
We study the immune response to filarial infections in different groups of individuals and have identified factors governing development of chronic, asymptomatic infection; factors related to pathogenesis of filarial disease (lymphedema and elephantiasis); correlates of protective immunity in putatively immune individuals and the regulation of immune responses in filarial infection and disease in India.
Soil-transmitted helminth infections (STH)
We perform immunological, clinical, epidemiological, and diagnostic studies in STH infections, mainly Strongyloidiasis and hookworm infections. We also perform high-throughput, multi-parallel molecular diagnostics, multi-parameter flow cytometry, and multi-omics approaches to study the immune response, natural history, and pathogenesis of STH infections in India. Our field studies provide extensive geo-spatial mapping of the prevalence of lymphatic filariasis and intestinal helminthiasis in South India, thereby contributing to epidemiological surveillance of these infections.
Helminth/Tuberculosis (TB) co-infection
We study the interaction of helminth infections as well as malnutrition with tuberculosis in an endemic setting in India. Our work has uncovered a major deleterious effect of helminth infections on host immunity to TB (potentially promoting progression to TB disease) and an association with heightened disease severity and bacterial burdens in pulmonary and extrapulmonary tuberculosis (potentially worsening TB disease pathology).
Our work in India, which has the most TB cases worldwide (26% of the global TB burden) on TB infections and disease, has led to a deeper understanding of TB immunology to inform vaccine development, identified prognostic biomarkers to assess TB treatment response (and risk of developing disease), and discovered diagnostic biomarkers especially in paucibacillary forms (childhood and extrapulmonary) of TB, which are typically hard to diagnose. We have also worked on the role of conventional and unconventional T-cell subsets in immunity and as correlates of protection in TB; on immune markers predicting disease progression (from latent to active disease); and on identification of diagnostic biomarkers that stratify TB infection sites (pulmonary and extrapulmonary) and stages (latent, active, incipient, subclinical, incident).
Interaction between diabetes and tuberculosis
We have performed different studies to research the immunological interactions of tuberculosis with type 2 diabetes mellitus. We discovered that active pulmonary TB with diabetes is associated with exaggerated, hyperinflammatory responses, while latent TB with diabetes is associated with diminished protective T cell and cytokine responses. We have elucidated the mechanism by which diabetes regulates immune responses in latent and active TB and identified predictive biomarkers for this interaction. We have also examined the effect of pre-diabetes on the host immune responses to latent and active TB. In addition, we have uncovered a role for TB in promoting the progression of pre-diabetes to diabetes and for promoting diabetes associated complications in comorbid individuals.
Interaction between diabetes and helminth infections
We have studied the immunological interactions of helminth infections with type 1 and type 2 diabetes mellitus. We have elucidated the helminth induced modulation of immune and inflammatory responses including cytokines, chemokines, adipokines, growth factors in type 2 diabetes mellitus and demonstrated that helminths have a protective effect against the pathogenesis of diabetes mellitus and its complications.
We have performed extensive studies on the immune responses in TB lymphadenitis, one of the most common extrapulmonary manifestations of TB and identified factors related to its pathogenesis. We have also identified various biomarkers of TB lymphadenitis in adults as well as in other extrapulmonary manifestations of TB in children.
Our group studies the interface of helminth infections and HIV, as well as latent TB and HIV, and has elucidated the effect of co-infection on HIV-associated immune responses. We have also elucidated the impact of HIV on systemic inflammation in pregnancy and the association of maternal inflammation with birth outcomes and infant growth in pregnant women with HIV and described the association of microbial translocation and intestinal dysbiosis with preterm birth in HIV-infected pregnant women.
We are studying the efficacy and immunology of Bacille Calmette-Guérin (BCG) in protecting against COVID-19 and other inflammatory disorders in elderly individuals. Our work has demonstrated a protective effect of BCG vaccine against inflammaging in elderly individuals. We have also identified the kinetics and durability of humoral and T-cell immunity in Covaxin (a whole virus inactivated SARS-CoV2 vaccine) recipients, as well as the innate and adaptive responses engendered by Covishield (an adenoviral vector encoded recombinant spike protein vaccine) in vaccine recipients in India.
We work on elucidating the pathogenesis and immune responses in multi-system inflammatory syndrome in children (MIS-C) in children, acute COVID-19 in children, and acute and convalescent COVID-19 in adults. Our group has identified novel biomarkers that can distinguish MIS-C from other clinically overlapping syndromes including Kawasaki disease. We are currently investigating the effect of co-infections such as helminths, other viral infections, and TB on immune responses to SARS-CoV2 infection and COVID-19 pathogenesis.