Abstract
Autism spectrum disorders (ASD) are characterized by impairment in social interactions, communication deficits, and restricted repetitive interests and behaviors. Recent evidence has suggested that impairments of innate immunity may play an important role in ASD. To test this hypothesis, we isolated peripheral blood monocytes from 17 children with ASD and 16 age-matched typically developing (TD) controls and stimulated these cell cultures in vitro with distinct toll-like receptors (TLR) ligands: TLR 2 (lipoteichoic acid; LTA), TLR 3 (poly I:C), TLR 4 (lipopolysaccharide; LPS), TLR 5 (flagellin), and TLR 9 (CpG-B). Supernatants were harvested from the cell cultures and pro-inflammatory cytokine responses for IL-1β, IL-6, IL-8, TNFα, MCP-1, and GM-CSF were determined by multiplex Luminex analysis. After in vitro challenge with TLR ligands, differential cytokine responses were observed in monocyte cultures from children with ASD compared with TD control children. In particular, there was a marked increase in pro-inflammatory IL-1β, IL-6, and TNFα responses following TLR 2, and IL-1β response following TLR 4 stimulation in monocyte cultures from children with ASD (p < 0.04). Conversely, following TLR 9 stimulation there was a decrease in IL-1β, IL-6, GM-CSF, and TNFα responses in monocyte cell cultures from children with ASD compared with controls (p < 0.05). These data indicate that, monocyte cultures from children with ASD are more responsive to signaling via select TLRs. As monocytes are key regulators of the immune response, dysfunction in the response of these cells could result in long-term immune alterations in children with ASD that may lead to the development of adverse neuroimmune interactions and could play a role in the pathophysiology observed in ASD.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 64-71 |
| Number of pages | 8 |
| Journal | Brain, Behavior, and Immunity |
| Volume | 24 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2010 |
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Keywords
- ASD
- Autism
- Cytokines
- Inflammation
- Monocytes
- Toll-like receptors
ASJC Scopus subject areas
- Immunology
- Behavioral Neuroscience
- Endocrine and Autonomic Systems
Cite this
Differential monocyte responses to TLR ligands in children with autism spectrum disorders. / Enstrom, Amanda M.; Onore, Charity E.; Van de Water, Judith A; Ashwood, Paul.
In: Brain, Behavior, and Immunity, Vol. 24, No. 1, 01.2010, p. 64-71.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differential monocyte responses to TLR ligands in children with autism spectrum disorders
AU - Enstrom, Amanda M.
AU - Onore, Charity E.
AU - Van de Water, Judith A
AU - Ashwood, Paul
PY - 2010/1
Y1 - 2010/1
N2 - Autism spectrum disorders (ASD) are characterized by impairment in social interactions, communication deficits, and restricted repetitive interests and behaviors. Recent evidence has suggested that impairments of innate immunity may play an important role in ASD. To test this hypothesis, we isolated peripheral blood monocytes from 17 children with ASD and 16 age-matched typically developing (TD) controls and stimulated these cell cultures in vitro with distinct toll-like receptors (TLR) ligands: TLR 2 (lipoteichoic acid; LTA), TLR 3 (poly I:C), TLR 4 (lipopolysaccharide; LPS), TLR 5 (flagellin), and TLR 9 (CpG-B). Supernatants were harvested from the cell cultures and pro-inflammatory cytokine responses for IL-1β, IL-6, IL-8, TNFα, MCP-1, and GM-CSF were determined by multiplex Luminex analysis. After in vitro challenge with TLR ligands, differential cytokine responses were observed in monocyte cultures from children with ASD compared with TD control children. In particular, there was a marked increase in pro-inflammatory IL-1β, IL-6, and TNFα responses following TLR 2, and IL-1β response following TLR 4 stimulation in monocyte cultures from children with ASD (p < 0.04). Conversely, following TLR 9 stimulation there was a decrease in IL-1β, IL-6, GM-CSF, and TNFα responses in monocyte cell cultures from children with ASD compared with controls (p < 0.05). These data indicate that, monocyte cultures from children with ASD are more responsive to signaling via select TLRs. As monocytes are key regulators of the immune response, dysfunction in the response of these cells could result in long-term immune alterations in children with ASD that may lead to the development of adverse neuroimmune interactions and could play a role in the pathophysiology observed in ASD.
AB - Autism spectrum disorders (ASD) are characterized by impairment in social interactions, communication deficits, and restricted repetitive interests and behaviors. Recent evidence has suggested that impairments of innate immunity may play an important role in ASD. To test this hypothesis, we isolated peripheral blood monocytes from 17 children with ASD and 16 age-matched typically developing (TD) controls and stimulated these cell cultures in vitro with distinct toll-like receptors (TLR) ligands: TLR 2 (lipoteichoic acid; LTA), TLR 3 (poly I:C), TLR 4 (lipopolysaccharide; LPS), TLR 5 (flagellin), and TLR 9 (CpG-B). Supernatants were harvested from the cell cultures and pro-inflammatory cytokine responses for IL-1β, IL-6, IL-8, TNFα, MCP-1, and GM-CSF were determined by multiplex Luminex analysis. After in vitro challenge with TLR ligands, differential cytokine responses were observed in monocyte cultures from children with ASD compared with TD control children. In particular, there was a marked increase in pro-inflammatory IL-1β, IL-6, and TNFα responses following TLR 2, and IL-1β response following TLR 4 stimulation in monocyte cultures from children with ASD (p < 0.04). Conversely, following TLR 9 stimulation there was a decrease in IL-1β, IL-6, GM-CSF, and TNFα responses in monocyte cell cultures from children with ASD compared with controls (p < 0.05). These data indicate that, monocyte cultures from children with ASD are more responsive to signaling via select TLRs. As monocytes are key regulators of the immune response, dysfunction in the response of these cells could result in long-term immune alterations in children with ASD that may lead to the development of adverse neuroimmune interactions and could play a role in the pathophysiology observed in ASD.
KW - ASD
KW - Autism
KW - Cytokines
KW - Inflammation
KW - Monocytes
KW - Toll-like receptors
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UR - http://www.scopus.com/inward/citedby.url?scp=71749094505&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2009.08.001
DO - 10.1016/j.bbi.2009.08.001
M3 - Article
C2 - 19666104
AN - SCOPUS:71749094505
VL - 24
SP - 64
EP - 71
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
SN - 0889-1591
IS - 1
ER -