New study aimed to assess how Dectin-1 functions in myeloid cells among various cohorts of individuals.

A new research paper was published on the cover of Aging, Dectin-1, an innate immune receptor specialised in detecting and binding β-1,3/1,6 glucans found on fungi, was the focus of a recent research investigation conducted by a team of scientists from Yale University. Their study aimed to assess how Dectin-1 functions in myeloid cells among various cohorts of individuals, both HIV-positive and HIV-negative, encompassing both young and older adults.

The study confirmed that the HIV-positive and HIV-negative groups exhibited similar characteristics in terms of age, gender distribution, and the prevalence of comorbidities such as diabetes, metabolic syndrome, cardiovascular disease, and pulmonary disease.

Upon stimulating monocytes with β-D-glucans, researchers observed a pro-inflammatory response in monocytes from HIV-infected individuals, marked by elevated levels of IL-12, TNF-α, and IL-6. Additionally, some age-related increases in cytokine levels were also noted. Dendritic cells exhibited a remarkable increase in IFN-α production associated with HIV infection. These heightened cytokine responses correlated with an increase in the expression of Dectin-1 on the surfaces of both monocytes and dendritic cells, a phenomenon observed in individuals with both HIV and advancing age.

Further analysis of differential gene expression revealed that HIV-positive older adults displayed a unique gene signature compared to other cohorts. This signature was characterised by a robust TNF-α and coagulation response that was elevated at baseline, a sustained IFN-α and IFN-γ response, and an activated dendritic cell signature/M1 macrophage signature following Dectin-1 stimulation.

The study also observed a substantial upregulation of MTORC1 signalling in response to Dectin-1 stimulation across all cohorts, with a more pronounced increase observed in the HIV-Older cohort, both during stimulation and at baseline. In summary, this research underscores the distinct immune profile exhibited by the HIV-positive older population when subjected to Dectin-1 stimulation. This unique signature could contribute to the pro-inflammatory environment associated with both HIV infection and the ageing process.