Dual TLR2/9 Recognition of Herpes Simplex Virus Infection Is Required for Recruitment and Activation of Monocytes and NK Cells and Restriction of Viral Dissemination to the Central Nervous System
Autor: | Ajit Mahadev Patil, Ferdaus Mohd Altaf Hossain, Sung Ok Park, Seong Kug Eo, Erdenebileg Uyangaa, Koanhoi Kim, Bumseok Kim, Jin Young Choi |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
Central Nervous System
0301 basic medicine lcsh:Immunologic diseases. Allergy Immunology NK cells CCL2 Biology Lymphocyte Activation medicine.disease_cause Mice 03 medical and health sciences Immune system medicine Animals Immunology and Allergy Encephalitis Viral dendritic cells Immunity Mucosal Original Research Mice Knockout Mice Inbred BALB C Toll-like receptor Monocyte TLR9 Herpes Simplex Viral Load herpes simplex virus Immunity Innate Toll-Like Receptor 2 Mucosal Infection Killer Cells Natural TLR2 030104 developmental biology medicine.anatomical_structure Herpes simplex virus Toll-Like Receptor 9 Vagina Cytokines toll-like receptor Female monocytes lcsh:RC581-607 |
Zdroj: | Frontiers in Immunology, Vol 9 (2018) Frontiers in Immunology |
ISSN: | 1664-3224 |
Popis: | The importance of TLR2 and TLR9 in the recognition of infection with herpes simplex virus (HSV) and HSV-caused diseases has been described, but some discrepancies remain concerning the benefits of these responses. Moreover, the impact of TLR2/9 on innate and adaptive immune responses within relevant mucosal tissues has not been elucidated using natural mucosal infection model of HSV. Here, we demonstrate that dual TLR2/9 recognition is essential to provide resistance against mucosal infection with HSV via an intravaginal route. Dual TLR2/9 ablation resulted in the highly enhanced mortality with exacerbated symptoms of encephalitis compared with TLR2 or TLR9 deficiency alone, coinciding with highly increased viral load in central nervous system tissues. TLR2 appeared to play a minor role in providing resistance against mucosal infection with HSV, since TLR2-ablated mice showed higher survival rate compared with TLR9-ablated mice. Also, the high mortality in dual TLR2/9-ablated mice was closely associated with the reduction in early monocyte and NK cell infiltration in the vaginal tract (VT), which was likely to correlate with low expression of cytokines and CCR2 ligands (CCL2 and CCL7). More interestingly, our data revealed that dual TLR2/9 recognition of HSV infection plays an important role in the functional maturation of TNF-α and iNOS-producing dendritic cells (Tip-DCs) from monocytes as well as NK cell activation in VT. TLR2/9-dependent maturation of Tip-DCs from monocytes appeared to specifically present cognate Ag, which effectively provided functional effector CD4+ and CD8+ T cells specific for HSV Ag in VT and its draining lymph nodes. TLR2/9 expressed in monocytes was likely to directly facilitate Tip-DC-like features after HSV infection. Also, dual TLR2/9 recognition of HSV infection directly activated NK cells without the aid of dendritic cells through activation of p38 MAPK pathway. Taken together, these results indicate that dual TLR2/9 recognition plays a critical role in providing resistance against mucosal infection with HSV, which may involve a direct regulation of Tip-DCs and NK cells in VT. Therefore, our data provide a more detailed understanding of TLR2/9 role in conferring antiviral immunity within relevant mucosal tissues after mucosal infection with HSV. |
Databáze: | OpenAIRE |
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