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Target Concepts:
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Query: UMLS:C0033036 (
APC
)
10,214
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The regulation of innate immune responses during viral infection is a crucial step to promote antiviral reactions. Recent studies have drawn attention to a strong relationship of pathogen-associated molecular pattern recognition with autophagy for activation of
APC
function. Our initial observations indicated that autophagosomes formed in response to respiratory syncytial virus (RSV) infection of dendritic cells (DC). To further investigate whether RSV-induced DC activation and innate cytokine production were associated with autophagy, we used several methods to block autophagosome formation. Using 3-MA, small interfering RNA inhibition of LC3, or Beclin(+/-) mouse-derived DC, studies established a relationship between RSV-induced autophagy and enhanced type I IFN, TNF, IL-6, and IL-12p40 expression. Moreover, autophagosome formation induced by starvation also promoted innate cytokine expression in DC. The induction of starvation-induced autophagy in combination with
RSV infection
synergistically enhanced DC cytokine expression that was blocked by an autophagy inhibitor. The latter synergistic responses were differentially altered in DC from MyD88(-/-) and TRIF(-/-) mice, supporting the concept of autophagy-mediated TLR signaling. In addition, blockade of autophagy in RSV-infected DC inhibited the maturation of DC as assessed by MHC class II and costimulatory molecule expression. Subsequently, we demonstrated that inhibition of autophagy in DC used to stimulate primary OVA-induced and secondary RSV-infected responses significantly attenuated cytokine production by CD4(+) T cells. Thus, these studies have outlined that autophagy in DC after
RSV infection
is a crucial mechanism for driving innate cytokine production, leading to altered acquired immune responses.
...
PMID:Autophagy-mediated dendritic cell activation is essential for innate cytokine production and APC function with respiratory syncytial virus responses. 2191 4
Regulatory T (T
reg
) cells establish tolerance, prevent inflammation at mucosal surfaces, and regulate immunopathology during infectious responses. Recent studies have shown that Delta-like ligand 4 (Dll4) was upregulated on
APC
after respiratory syncytial virus (RSV) infection, and its inhibition leads to exaggerated immunopathology. In the present study, we outline the role of Dll4 in T
reg
cell differentiation, stability, and function in
RSV infection
. We found that Dll4 was expressed on CD11b
+
pulmonary dendritic cells in the lung and draining lymph nodes in wild-type BALB/c mice after
RSV infection
. Dll4 neutralization exacerbated RSV-induced disease pathology, mucus production, group 2 innate lymphoid cell infiltration, IL-5 and IL-13 production, as well as IL-17A
+
CD4 T cells. Dll4 inhibition decreased the abundance of CD62L
hi
CD44
lo
Foxp3
+
central T
reg
cells in draining lymph nodes. The RSV-induced disease was accompanied by an increase in Th17-like effector phenotype in Foxp3
+
T
reg
cells and a decrease in granzyme B expression after Dll4 blockade. Finally, Dll4-exposed induced T
reg
cells maintained the CD62L
hi
CD44
lo
central T
reg
cell phenotype, had increased Foxp3 expression, became more suppressive, and were resistant to Th17 skewing in vitro. These results suggest that Dll4 activation during differentiation sustained T
reg
cell phenotype and function to control
RSV infection
.
...
PMID:Notch Ligand Delta-like 4 Promotes Regulatory T Cell Identity in Pulmonary Viral Infection. 2807 98
