A healthy immune system protects against diseases and maintains immune balance. Yet, this resilience is often compromised in the very young or old, or those with chronic infectious diseases, cancers, autoimmune, and metabolic disorders. These individuals are more susceptible to severe diseases and often have a reduced response to vaccines. Research in the Arunachalam lab aims to uncover how the steady-state immune system, i.e., the baseline immune state, is altered in these individuals leading to weakened immune responses to infection and vaccines. Current projects focus on HIV and aging as model systems.

Understanding the impacts of aging with chronic infectious diseases on the human immune system

Aging is associated with immune dysfunction. Whether aging with HIV exacerbates immune dysfunction, and causes premature aging is a focus of this project. The increased incidence of cardiovascular, renal, and other age-related complications in people living with HIV suggests the likelihood of premature aging and enhanced immune dysfunction. Employing state-of-the-art multiomic technologies at a single-cell level in combination with functional immune assays, we are investigating how low-level systemic inflammation observed in chronic HIV infection exacerbates immune dysfunction associated with aging, in particular the innate immune system. This work lays the foundation for further exploration into the biological underpinnings of the immune trajectory of aging with HIV infection.

Harnessing innate immunity for HIV prevention and cure using systems biology approaches

Every pathogen, and indeed any stimulus to the immune system, evokes an innate immune response. While numerous studies have documented these responses to HIV and other pathogens, their biological significance and prognostic potential remain largely unexplored. In this project, we are investigating innate immune responses in HIV patients and SIV-infected macaques under antiretroviral therapy to define immune signatures of chronic HIV infection and viral reactivation.

Systems immunology of vaccine adjuvants

In collaboration with Prof. Bali Pulendran, we are building a multiomic atlas of immune responses induced by a subunit protein vaccine formulated with various adjuvants. The study involves a cross-species comparative analysis in mice, non-human primates, and human organoids to assess immune responses to vaccine adjuvants across different species.