Table 4 pDC activation and functions during local viral infections
From: The role of plasmacytoid dendritic cells (pDCs) in immunity during viral infections and beyond
Virus; host | Infection route | pDC contribution to antiviral immune functions | |||
|---|---|---|---|---|---|
IFN-I production | Host resistance | Intrinsic, innate or adaptive immunity | |||
Contribution1 | Site; method2 | ||||
VSV; mouse | footpad | Major, with infected SCM [105] | LN homogenate; ELISA | Contributes to immunity, increased VSV propagation from popliteal to inguinal LN upon pDC depletion in DT-treated BDCA2-hDTR mice [106] | ND |
MVA; mouse | footpad | Minor [106] | LN homogenate; ELISA | ND | Contributes to adaptive immunity, reduced CD8 T-cell numbers and impaired cDC1 activation upon pDC depletion in BDCA2-hDTR mice [106] |
ECTV; mouse | Minor [107] | LNs; intracellular FC | Putative protective role, slighty decreased survival upon Bst2+ cell depletion | ND | |
HSV-1; mouse | Intracorneal | Major [108] | Cornea; qRT‒PCR for Ifna | Major protective role, increased viral load, morbidity and mortality upon pDC depletion in BDCA2-hDTR mice [108] | Reinforcement of intrinsic immunity, corneal nerve infection and corneal homogenate viral titers are increased already on day 1 postinfection upon local pDC depletion in BDCA2-hDTR mice Contributes to adaptive immunity, pDCs preserve CD4 Tregs in the draining LN [108] |
IAV; mouse | intranasal | Controversial Minor [114] | Spleen homogenate [110], lung homogenate [109, 112], lung [111, 113, 115, 116]; BAL [111, 114]; ELISA, qRT‒PCR [111, 113, 115, 116] | Controversial Putatively protective role, Bst2+ cell depletion increased viral titers in Mx1+ C57BL/6 mice [117] Putatively deleterious role, Bst2+ cell depletion slightly decreased viral titers in Mx1-/- BALB/c mice [112, 115] and reduced their morbidity and mortality [115]; Bst2+ cell depletion reduced the morbidity and mortality of 129S mice [111, 116] Redundant role, lack of pDCs in IkarosL/L or anti-Bst2-treated mice did not change viral titers and survival [110, 114] | Putatively contributes to innate immunity and inflammation, with contrasting results in anti-Bst2-treated mice: higher numbers of monocytes and production of TNF and IL-6 [112] versus reduced numbers of monocytes and production of inflammatory cytokines [111, 116] Putatively contributes to modulate adaptive immunity: reduction of anti-IAV antibodies in anti-Bst2-treated C57BL/6 [114], delay in CD8 T-cell recruitment in IkarosL/L mice [110], possible induction of IAV-specific CD8 T-cell apoptosis in the draining LN by FASL+ pDCs [115] |
SARS-CoV1; mouse | intranasal | Major [118] | Ex vivo isolated lung Siglech+ cells; qRT‒PCR for Ifna and Ifnb1 [118] | Putative deleterious role, Bst2+ cell depletion diminishes lung lesions and inflammation while increasing survival | ND |
MERS-CoV; mouse | intranasal | Major [119] | Lung; qRT‒PCR (indirect evidence: decrease in Ifna and Ifnb1 expression in Tlr7-KO mice) [119] | ND, but it is predicted to depend on the kinetics of pDC IFN-I production, since administration of exogenous IFN-β is beneficial early (between 6 h and 24 h postinfection) but deleterious later (at 2 days or 4 days postinfection) [119] | ND |
NDV; mouse | intranasal | ND | ND | ||
RSV; mouse | intranasal | Minor [109] | Lung; ELISA, in situ hybridization with Ifna4 probe | ND | ND |
PVM; mouse | intranasal | Major [120] | BAL, ELISA | Beneficial role. pDC depletion in BDCA2-hDTR neonates increased viral load and bronchiolitis, as well as predisposition to asthma upon reinfection in adulthood. | Contributes to immunity. pDC depletion in BDCA2-hDTR mice increased pro-inflammatory neutrophils, eosinophils and cytokines, and reduced NRP+ Treg [120] |
MCV; human | cutaneous | Contributing [121] | Skin biopsies; qRT‒PCR for Ifna | ND | ND |
HSV-2; mouse | vaginal | Minor [92] | Vaginal homogenate; ELISA | No difference in viral titers and mouse survival upon pDC depletion in BDCA2-DTR mice [92] | ND |
RV; mouse, piglet, human | Gut | In vitro; intracellular FC of RV-stimulated human PBMCs, IFN neutralization in RV-stimulated mouse pDC/B-cell cocultures [122] Intestinal cells from infected piglets; intracellular FC [123] | Protective role, increased viral shedding upon pDC depletion in anti-Bst2-treated or BDCA2-DTR mice, or upon in vivo inhibition of pDC IFN-I production upon anti-Siglech Ab administration [122] | Promotion of antiviral IgG and IgA antibodies in the gut, since these responses are decreased upon pDC depletion or inhibition, explaining increased viral shedding in these experimental conditions [122] | |
