Associations between Monocyte and T Cell Cytokine Profiles in Autism Spectrum Disorders: Effects of Dysregulated Innate Immune Responses on Adaptive Responses to Recall Antigens in a Subset of ASD Children

Abstract

Changes in monocyte cytokine production with toll like receptor (TLR) agonists in subjects with autism spectrum disorders (ASD) were best reflected by the IL-1β/IL-10 ratios in our previous research. The IL-1β/IL-10 based subgrouping (low, normal, and high) of ASD samples revealed marked differences in microRNA expression, and mitochondrial respiration. However, it is unknown whether the IL-1β/IL-10 ratio based subgrouping is associated with changes in T cell cytokine profiles or monocyte cytokine profiles with non-TLR agonists. In ASD (n = 152) and non-ASD (n = 41) subjects, cytokine production by peripheral blood monocytes (PBMo) with TLR agonists and β-glucan, an inflammasome agonist, and T cell cytokine production by peripheral blood mononuclear cells (PBMCs) with recall antigens (Ags) (food and candida Ags) were concurrently measured. Changes in monocyte cytokine profiles were observed with β-glucan in the IL-1β/IL-10 ratio based ASD subgroups, along with changes in T cell cytokine production and ASD subgroup-specific correlations between T cell and monocyte cytokine production. Non-ASD controls revealed considerably less of such correlations. Altered innate immune responses in a subset of ASD children are not restricted to TLR pathways and correlated with changes in T cell cytokine production. Altered trained immunity may play a role in the above described changes.