Age-dependent changes in innate immune phenotype and function in rhesus macaques (Macaca mulatta)

Area of Science:

• Immunology
• Aging Research
• Primate Models

Background:

• Immune senescence in the elderly increases infection susceptibility.
• Age-related adaptive immunity decline is known, but innate immunity aging is less understood.
• Nonhuman primates, like rhesus macaques, are valuable models for aging research.

Purpose of the Study:

• To investigate age-related changes in innate immune cell frequency and function in rhesus macaques.
• To analyze the expression of pattern recognition receptors (PRRs) and signaling molecules.
• To determine how age affects cytokine responses of monocytes and dendritic cells (DCs) to PRR agonists.

Main Methods:

• Examined innate immune cell frequencies in young versus aged rhesus macaques.
• Assessed expression of PRRs and innate signaling molecules.
• Stimulated monocytes and DCs with PRR agonists to measure cytokine production (TNFα, IL-6, IFNα).
• Analyzed plasma cytokine levels.

Main Results:

• Increased frequency of myeloid dendritic cells (mDCs) in aged macaques.
• Reduced cytokine responses (TNFα, IL-6, IFNα) in aged mDCs upon stimulation with TLR agonists (LPS, FSL-1, ODN2006), except for monocyte TNFα to LPS which increased.
• Differential expression of PRRs (TLR4, TLR5) and regulators (SARM, AIM2, RIG-I) based on age.

Conclusions:

• Innate immune cell phenotype and function are significantly modulated by age in rhesus macaques.
• Age-dependent changes in innate immunity contribute to differential immune function in aged individuals.
• Findings provide mechanistic insights into increased infection susceptibility in the elderly.