High-Resolution Profiling of Innate Immune Responses by Porcine Dendritic Cell Subsets in vitro and in vivo

Marek’s disease virus (MDV) is an alphaherpesvirus that causes Marek’s disease, a malignant lymphoproliferative disease of domestic chickens. While MDV vaccines protect animals from clinical disease, they do not provide sterilizing immunity and allow field strains to circulate and evolve in vaccinated flocks. Therefore, there is a need for improved vaccines and for a better understanding of innate and adaptive immune responses against MDV infections. Interferons (IFNs) play important roles in the innate immune defenses against viruses and induce upregulation of a cellular antiviral state. In this report, we quantified the potent antiviral effect of IFNα and IFNγ against MDV infections in vitro. Moreover, we demonstrate that both cytokines can delay Marek’s disease onset and progression in vivo. Additionally, blocking of endogenous IFNα using a specific monoclonal antibody, in turn, accelerated disease. In summary, our data reveal the effects of IFNα and IFNγ on MDV infection and improve our understanding of innate immune responses against this oncogenic virus.

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Induction of Innate Immune Responses by SIV In Vivo and In Vitro: Differential Expression and Function of RIG-I and MDA5

The Journal of Infectious Diseases ◽

10.1093/infdis/jir469 ◽

2011 ◽

Vol 204 (7) ◽

pp. 1104-1114 ◽

Cited By ~ 15

Author(s):

Juliene G. Co ◽

Kenneth W. Witwer ◽

Lucio Gama ◽

M. Christine Zink ◽

Janice E. Clements

Keyword(s):

Immune Responses ◽

Differential Expression ◽

Innate Immune ◽

Innate Immune Responses ◽

And Function

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Pneumolysin, PspA, and PspC Contribute to Pneumococcal Evasion of Early Innate Immune Responses during Bacteremia in Mice

Infection and Immunity ◽

10.1128/iai.01727-06 ◽

2007 ◽

Vol 75 (4) ◽

pp. 2067-2070 ◽

Cited By ~ 38

Author(s):

Lisa R. Quin ◽

Quincy C. Moore ◽

Larry S. McDaniel

Keyword(s):

Immune Responses ◽

Virulence Factors ◽

Innate Immune ◽

Blood Clearance ◽

Innate Immune Responses

ABSTRACTThe pneumococcal virulence factors include capsule, PspA, PspC, and Ply. Cytometric analysis demonstrated that the greatest levels of C3 deposition were on a ΔplyPspA−PspC−mutant. Also, Ply, PspA, and PspC expression resulted in C3 degradation in vitro and in vivo. Finally, blood clearance assays demonstrated that there was enhanced clearance of ΔplyPspA−PspC−pneumococci compared to the clearance of nonencapsulated pneumococci.

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Cocaine-induced release of CXCL10 from pericytes regulates monocyte transmigration into the CNS

The Journal of Cell Biology ◽

10.1083/jcb.201712011 ◽

2019 ◽

Vol 218 (2) ◽

pp. 700-721 ◽

Cited By ~ 9

Author(s):

Fang Niu ◽

Ke Liao ◽

Guoku Hu ◽

Susmita Sil ◽

Shannon Callen ◽

...

Keyword(s):

Immune Responses ◽

Innate Immune ◽

Innate Immune Responses ◽

Active Components ◽

Barrier Integrity ◽

Enhanced Secretion ◽

First Time ◽

The Brain

Cocaine is known to facilitate the transmigration of inflammatory leukocytes into the brain, an important mechanism underlying neuroinflammation. Pericytes are well-recognized as important constituents of the blood–brain barrier (BBB), playing a key role in maintaining barrier integrity. In the present study, we demonstrate for the first time that exposure of human brain vascular pericytes to cocaine results in enhanced secretion of CXCL10, leading, in turn, to increased monocyte transmigration across the BBB both in vitro and in vivo. This process involved translocation of σ-1 receptor (σ-1R) and interaction of σ-1R with c-Src kinase, leading to activation of the Src–PDGFR-β–NF-κB pathway. These findings imply a novel role for pericytes as a source of CXCL10 in the pericyte–monocyte cross talk in cocaine-mediated neuroinflammation, underpinning their role as active components of the innate immune responses.

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Toll-like receptor 9 mediates innate immune activation by the malaria pigment hemozoin

Journal of Experimental Medicine ◽

10.1084/jem.20041836 ◽

2005 ◽

Vol 201 (1) ◽

pp. 19-25 ◽

Cited By ~ 412

Author(s):

Cevayir Coban ◽

Ken J. Ishii ◽

Taro Kawai ◽

Hiroaki Hemmi ◽

Shintaro Sato ◽

...

Keyword(s):

Immune Responses ◽

Immune Activation ◽

Interleukin 1 ◽

Innate Immune ◽

Dependent Manner ◽

Innate Immune Responses ◽

Toll Like Receptor ◽

Innate Immune Activation

Malaria parasites within red blood cells digest host hemoglobin into a hydrophobic heme polymer, known as hemozoin (HZ), which is subsequently released into the blood stream and then captured by and concentrated in the reticulo-endothelial system. Accumulating evidence suggests that HZ is immunologically active, but the molecular mechanism(s) through which HZ modulates the innate immune system has not been elucidated. This work demonstrates that HZ purified from Plasmodium falciparum is a novel non-DNA ligand for Toll-like receptor (TLR)9. HZ activated innate immune responses in vivo and in vitro, resulting in the production of cytokines, chemokines, and up-regulation of costimulatory molecules. Such responses were severely impaired in TLR9−/− and myeloid differentiation factor 88 (MyD88)−/−, but not in TLR2, TLR4, TLR7, or Toll/interleukin 1 receptor domain–containing adaptor-inducing interferon β−/− mice. Synthetic HZ, which is free of the other contaminants, also activated innate immune responses in vivo in a TLR9-dependent manner. Chloroquine (CQ), an antimalarial drug, abrogated HZ-induced cytokine production. These data suggest that TLR9-mediated, MyD88-dependent, and CQ-sensitive innate immune activation by HZ may play an important role in malaria parasite–host interactions.

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Viable Borrelia burgdorferi Enhances Interleukin-10 Production and Suppresses Activation of Murine Macrophages

Infection and Immunity ◽

10.1128/iai.01404-07 ◽

2007 ◽

Vol 76 (3) ◽

pp. 1153-1162 ◽

Cited By ~ 34

Author(s):

John J. Lazarus ◽

Maria A. Kay ◽

Akisha L. McCarter ◽

R. Mark Wooten

Keyword(s):

Borrelia Burgdorferi ◽

Immune Responses ◽

Culture Medium ◽

Interleukin 10 ◽

Innate Immune ◽

Innate Immune Responses ◽

Wild Type ◽

Adaptive Immune

ABSTRACT Although it is capable of eliciting strong innate and adaptive immune responses, Borrelia burgdorferi often evades immune clearance through largely unknown mechanisms. Our previous studies determined that infected interlukin-10−/− (IL-10−/−) mice show significantly lower B. burgdorferi levels than wild-type (B6) mice and that IL-10 inhibits innate immune responses critical for controlling B. burgdorferi infection. To determine whether virulent B. burgdorferi preferentially enhances IL-10 production, we developed an in vitro coculture medium (RPMI.B) in which both B. burgdorferi and primary macrophages (Mφs) remain viable. B. burgdorferi grew at similar rates and was able to regulate expression of immunoreactive proteins with similar kinetics in RPMI.B and in traditional BSK medium; in contrast, B. burgdorferi cultured in conventional tissue culture medium (RPMI) rapidly lost viability. Coculture of viable B. burgdorferi in RPMI.B with Mφs resulted in more rapid and significant increases in IL-10 transcripts and secreted proteins than coculture with nonviable B. burgdorferi in RPMI, which corresponded with decreased production of proinflammatory cytokines. Addition of live B. burgdorferi to Mφs in RPMI.B also elicited substantially higher IL-10 levels than heat-killed bacteria elicited, confirming that increased IL-10 production was not inherent to coculture in RPMI.B. Transfer of supernatants from B. burgdorferi-stimulated Mφs into naïve Mφ cultures resulted in suppressed activation upon subsequent stimulation with different bacterial agonists, and this suppression was obviated by IL-10-specific antibody. In vivo analyses determined that murine skin samples exhibited substantial upregulation of IL-10 within 24 h of injection of B. burgdorferi. Together, these results suggest that viable B. burgdorferi can suppress early Mφ responses during infection by causing increased release of IL-10.

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Regulation of TRIF-mediated innate immune response by K27-linked polyubiquitination and deubiquitination

Nature Communications ◽

10.1038/s41467-019-12145-1 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 9

Author(s):

Xin Wu ◽

Caoqi Lei ◽

Tian Xia ◽

Xuan Zhong ◽

Qing Yang ◽

...

Keyword(s):

Immune Responses ◽

Adaptor Protein ◽

Innate Immune ◽

Negative Regulator ◽

Type I Interferons ◽

Poly I:C ◽

Type I ◽

Innate Immune Responses

Abstract TIR domain-containing adaptor inducing interferon-β (TRIF) is an essential adaptor protein required for innate immune responses mediated by Toll-like receptor (TLR) 3- and TLR4. Here we identify USP19 as a negative regulator of TLR3/4-mediated signaling. USP19 deficiency increases the production of type I interferons (IFN) and proinflammatory cytokines induced by poly(I:C) or LPS in vitro and in vivo. Usp19-/- mice have more serious inflammation after poly(I:C) or LPS treatment, and are more susceptible to inflammatory damages and death following Salmonella typhimurium infection. Mechanistically, USP19 interacts with TRIF and catalyzes the removal of TRIF K27-linked polyubiquitin moieties, thereby impairing the recruitment of TRIF to TLR3/4. In addition, the RING E3 ubiquitin ligase complex Cullin-3-Rbx1-KCTD10 catalyzes K27-linked polyubiquitination of TRIF at K523, and deficiency of this complex inhibits TLR3/4-mediated innate immune signaling. Our findings thus reveal TRIF K27-linked polyubiquitination and deubiquitination as a critical regulatory mechanism of TLR3/4-mediated innate immune responses.

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