Cutting Edge: In Vivo Induction of Integrated HIV-1 Expression by Mycobacteria Is Critically Dependent on Toll-Like Receptor 2

Toll-like receptor 2 (TLR2) ligands are attracting increasing attention as prophylactic and immunotherapeutic agents against pathogens and tumors. We previously observed that a synthetic diacylated lipopeptide based on a surface protein of Mycoplasma agalactiae (Mag-Pam2Cys) strongly activated innate immune cells, including porcine monocyte-derived macrophages (moMΦ). In this study, we utilized confocal microscopy, flow cytometry, multiplex cytokine ELISA, and RT-qPCR to conduct a comprehensive analysis of the effects of scalar doses of Mag-Pam2Cys on porcine moMΦ. We observed enhanced expression of activation markers (MHC class I, MHC class II DR, CD25), increased phagocytotic activity, and release of IL-12 and proinflammatory cytokines. Mag-Pam2Cys also upregulated the gene expression of several IFN-α subtypes, p65, NOS2, and molecules with antimicrobial activities (CD14, beta defensin 1). Overall, our data showed that Mag-Pam2Cys polarized porcine macrophages towards a proinflammatory antimicrobial phenotype. However, Mag-Pam2Cys downregulated the expression of IFN-α3, six TLRs (TLR3, -4, -5, -7, -8, -9), and did not interfere with macrophage polarization induced by the immunosuppressive IL-10, suggesting that the inflammatory activity evoked by Mag-Pam2Cys could be regulated to avoid potentially harmful consequences. We hope that our in vitro results will lay the foundation for the further evaluation of this diacylated lipopeptide as an immunopotentiator in vivo.

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Interferon-β induced in female genital epithelium by HIV-1 glycoprotein 120 via Toll-like-receptor 2 pathway acts to protect the mucosal barrier

Cellular and Molecular Immunology ◽

10.1038/cmi.2017.168 ◽

2018 ◽

Vol 16 (2) ◽

pp. 178-194 ◽

Cited By ~ 7

Author(s):

Aisha Nazli ◽

Sara Dizzell ◽

Muhammad Atif Zahoor ◽

Victor H Ferreira ◽

Jessica Kafka ◽

...

Keyword(s):

Mucosal Barrier ◽

Toll Like Receptor ◽

Interferon Β ◽

Toll Like Receptor 2 ◽

Hiv 1 ◽

Female Genital

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Toll-Like Receptor 2 Promoter -196 to -174 Deletion Affects CD4 Levels Along Human Immunodeficiency Virus Infection Progression

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa327 ◽

2020 ◽

Vol 222 (12) ◽

pp. 2007-2011 ◽

Cited By ~ 1

Author(s):

Marina Laplana ◽

Maria Jose Bravo ◽

Marta Fernández-Fuertes ◽

Celia Ruiz-Garcia ◽

Emilio Alarcón-Martin ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Disease Progression ◽

Cox Regression ◽

Toll Like Receptor ◽

Cox Regression Analysis ◽

Immunodeficiency Virus ◽

Toll Like Receptor 2 ◽

Time Required ◽

Molecular Patterns ◽

Hiv 1

Abstract Toll-like receptor 2 (TLR2) plays a key role in innate immune response recognizing molecular patterns expressed by pathogens. rs111200466 is a TLR2 promoter insertion/deletion polymorphism with contradictory data about its role in human immunodeficiency virus type 1 (HIV-1) infection. We analyzed rs111200466 in HIV-1 disease progression and showed a correlation with a faster progression to the CD4+ < 200 cells/μL outcome for deletion allele carriers (Cox regression analysis: hazard ratio, 2.4 [95% confidence interval, 1.4–4]; P = .001). When naive patients with CD4+ < 200 cells/μL started antiretroviral treatment, rs111200466-deletion carriers showed a trend toward a slower, recovery rate (time required to reach CD4+ > 350 cells/μL; Cox P = .36). Our data suggest rs111200466 as a prognosis factor for HIV-1 disease progression.

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Studies on in vivo induction of HIV-1 envelope-specific cytotoxic T lymphocytes by synthetic peptides from the V3 loop region of HIV-1 IIIB gp120

Cellular Immunology ◽

10.1016/0008-8749(95)80031-d ◽

1995 ◽

Vol 160 (2) ◽

pp. 217-223 ◽

Cited By ~ 26

Author(s):

Pramod N. Nehete ◽

Kevin S. Casement ◽

Ralph B. Arlinghaus ◽

K.Jagannadha Sastry

Keyword(s):

T Lymphocytes ◽

Cytotoxic T Lymphocytes ◽

Synthetic Peptides ◽

V3 Loop ◽

Loop Region ◽

Hiv 1 ◽

In Vivo Induction

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Distinct Roles for MyD88 and Toll-Like Receptor 2 during Leishmania braziliensis Infection in Mice

Infection and Immunity ◽

10.1128/iai.00154-09 ◽

2009 ◽

Vol 77 (7) ◽

pp. 2948-2956 ◽

Cited By ~ 59

Author(s):

Diego A. Vargas-Inchaustegui ◽

Wendy Tai ◽

Lijun Xin ◽

Alison E. Hogg ◽

David B. Corry ◽

...

Keyword(s):

T Cells ◽

Protective Immunity ◽

Interleukin 12 ◽

Leishmania Braziliensis ◽

Toll Like Receptor ◽

Enhanced Resistance ◽

Toll Like Receptor 2 ◽

Resistance To Infection

ABSTRACT We have previously reported that Leishmania braziliensis infection can activate murine dendritic cells (DCs) and upregulate signaling pathways that are essential for the initiation of innate immunity. However, it remains unclear whether Toll-like receptors (TLRs) are involved in L. braziliensis-mediated DC activation. To address this issue, we generated bone marrow-derived DCs from MyD88−/− and TLR2−/− mice and examined their responsiveness to parasite infection. While wild-type DCs were efficiently activated to produce cytokines and prime naïve CD4+ T cells, L. braziliensis-infected MyD88−/− DCs exhibited less activation and decreased production of interleukin-12 (IL-12) p40. Furthermore, MyD88−/− mice were more susceptible to infection in that they developed larger and prolonged lesions compared to those in control mice. In sharp contrast, the lack of TLR2 resulted in an enhanced DC activation and increased IL-12 p40 production after infection. As such, L. braziliensis-infected TLR2−/− DCs were more competent in priming naïve CD4+ T cells in vitro than were their controls, findings which correlated with an increased gamma interferon production in vivo and enhanced resistance to infection. Our results suggest that while MyD88 is indispensable for the generation of protective immunity to L. braziliensis, TLR2 seems to have a regulatory role during infection.

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Serum amyloid A induces G-CSF expression and neutrophilia via Toll-like receptor 2

Blood ◽

10.1182/blood-2008-03-139923 ◽

2009 ◽

Vol 113 (2) ◽

pp. 429-437 ◽

Cited By ~ 109

Author(s):

Rong L. He ◽

Jian Zhou ◽

Crystal Z. Hanson ◽

Jia Chen ◽

Ni Cheng ◽

...

Keyword(s):

Serum Amyloid A ◽

Inflammatory Diseases ◽

Serum Amyloid ◽

Proteinase K ◽

In Vivo Studies ◽

Toll Like Receptor ◽

Amyloid A ◽

Toll Like Receptor 2

Abstract The acute-phase protein serum amyloid A (SAA) is commonly considered a marker for inflammatory diseases; however, its precise role in inflammation and infection, which often result in neutrophilia, remains ambiguous. In this study, we demonstrate that SAA is a potent endogenous stimulator of granulocyte colony-stimulated factor (G-CSF), a principal cytokine-regulating granulocytosis. This effect of SAA is dependent on Toll-like receptor 2 (TLR2). Our data demonstrate that, in mouse macrophages, both G-CSF mRNA and protein were significantly increased after SAA stimulation. The induction of G-CSF was blocked by an anti-TLR2 antibody and markedly decreased in the TLR2-deficient macrophages. SAA stimulation results in the activation of nuclear factor–κB and binding activity to the CK-1 element of the G-CSF promoter region. In vitro reconstitution experiments also support that TLR2 mediates SAA-induced G-CSF expression. In addition, SAA-induced secretion of G-CSF was sensitive to heat and proteinase K treatment, yet insensitive to polymyxin B treatment, indicating that the induction is a direct effect of SAA. Finally, our in vivo studies confirmed that SAA treatment results in a significant increase in plasma G-CSF and neutrophilia, whereas these responses are ablated in G-CSF– or TLR2-deficient mice.

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