Protective T-Cell-Based Immunity Induced in Neonatal Mice by a Single Replicative Cycle of Herpes Simplex Virus

Franchini, Marco; Abril, Carlos; Schwerdel, Cornelia; Ruedl, Christiane; Ackermann, Mathias; Suter, Mark

doi:10.1128/jvi.75.1.83-89.2001

Cited by 49 publications

(49 citation statements)

References 63 publications

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“…Viral particles were further purified by sucrose density gradient centrifugation, as described (21). Apart from HSV-1, disabled infectious single-cycle HSV-1 (HSV-1d), a mutated HSV-1 strain, was also used and was propagated and prepared as described (22). HSV-1d lacks the gene for glycoprotein H, needed for infection, and therefore this mutant virus performs only one cycle of infection (23).…”

Section: Methodsmentioning

confidence: 99%

Herpes simplex virus type-1 induces IFN-α production via Toll-like receptor 9-dependent and -independent pathways

Hochrein

Schlatter

O’Keeffe

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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398

332

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Type I IFN production in response to the DNA virus herpes simplex virus type-1 (HSV-1) is essential in controlling viral replication. We investigated whether plasmacytoid dendritic cells (pDC) were the major tissue source of IFN-␣, and whether the production of IFN-␣ in response to HSV-1 depended on Toll-like receptor 9 (TLR9). Total spleen cells or bone marrow (BM) cells, or fractions thereof, including highly purified pDC, from WT, TLR9, and MyD88 knockout mice were stimulated with known ligands for TLR9 or active HSV-1. pDC freshly isolated from both spleen and BM were the major source of IFN-␣ in response to oligodeoxynucleotides containing CpG motifs, but in response to HSV-1 the majority of IFN-␣ was produced by other cell types. Moreover, IFN-␣ production by non-pDC was independent of TLR9. The tissue source determined whether pDC responded to HSV-1 in a strictly TLR9-dependent fashion. Freshly isolated BM pDC or pDC derived from culture of BM precursors with FMS-like tyrosine kinase-3 ligand, produced IFN-␣ in the absence of functional TLR9, whereas spleen pDC did not. Heat treatment of HSV-1 abolished maturation and IFN-␣ production from all TLR9-deficient DC but not WT DC. Thus pDC and non-pDC produce IFN-␣ in response to HSV-1 via both TLR9-independent and -dependent pathways.

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Section: Methodsmentioning

confidence: 99%

Herpes simplex virus type-1 induces IFN-α production via Toll-like receptor 9-dependent and -independent pathways

Hochrein

Schlatter

O’Keeffe

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

398

332

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“…Neonates and infants also have a reduced or suboptimal capacity to mount an effective cell-mediated immunity in response to most vaccines (1,(3)(4)(5). However, introducing a vaccine Ag into the cytoplasm of APCs induces a significant CD8 CTL response even in neonates (3,6,7). Contrary to the induction of CTLs, Th1 (IFN-␥ producing) CD4 T cell responses have not only been difficult to induce in the neonate, but appear even more difficult to sustain (4,5,8,9).…”

Section: Induction Of Protective Immunity Tomentioning

confidence: 99%

Induction of Protective Immunity to Listeria monocytogenes in Neonates

Kollmann

Reikie

Blimkie

et al. 2007

The Journal of Immunology

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Neonates suffer unduly from infections and also respond suboptimally to most commonly used vaccines. However, a CD8 T cell response can be elicited in neonates if the Ag is introduced into the cytoplasm of APCs. Listeria monocytogenes (Lm) targets the cytoplasm of APC and is a strong CD8 and CD4 Th1-promoting vaccine vehicle in adult mice. We hypothesized that an attenuated strain of Lm would be safe and induce long-lasting protective immunity, even in neonates. We found that neonatal mice immunized only once with the attenuated strain ΔactA-Lm developed robust primary and secondary CD8 and CD4 Th1 responses and were fully protected from lethal challenge with virulent wild-type Lm without the need for a booster immunization. Furthermore, ΔactA-Lm expressing a heterologous recombinant Ag induced a strong CD8 and Th1 memory response to that Ag. Based on these data, we propose that ΔactA-Lm or derivatives thereof might serve as a vaccine vehicle for neonatal immunization.

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“…The ability of a virus to replicate has also been shown to affect the newborn cellular response, with viral replication required to induce Th1 responses [16]. Neonatal mice have been shown to mount a secondary CTL response upon rechallenge as adults after immunization at birth with a single-replicative-cycle HSV-1 mutant [17]. However, the development of the primary CD4 + cytokine response and of the CD8 + CTL response to HSV has not been defined in human or murine neonates at the site of T cell activation, the draining lymph nodes (LN).…”

Section: Introductionmentioning

confidence: 99%

HSV induces an early primary Th1 CD4 T cell response in neonatal mice, but reduced CTL activity at the time of the peak adult response

Evans

Jones

2005

Eur J Immunol

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Neonates are highly susceptible to HSV. In this study, we analyzed the primary neonatal cell-mediated response to HSV at the site of T cell activation, the draining lymph nodes (LN), and examined the effects of dose and the ability of HSV to replicate on the strength and character of this response. Neonatal mice mounted a predominantly Th1 cytokine (IFN-c) response at all doses of a replication-competent thymidine kinase-negative HSV-2 strain (186DKpn) and at high doses of a replication-defective HSV-2 virus (dl5-29, UL5-/UL29 -). Both neonates and adults showed increased production of Th2 cytokines (IL-4 and/or IL-5) at high doses of the replication-defective or inactivated HSV strains. An age-dependent difference in the strength of the Th1 response was noted, with neonates mounting adult-like responses at low but not high doses of HSV. Neonatal mice also showed impaired CD8 + T cell activation and reduced HSV-specific CTL effector function at the time of the peak adult response. These studies are the first to highlight the impaired primary neonatal T cell response to HSV in the LN.

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Protective T-Cell-Based Immunity Induced in Neonatal Mice by a Single Replicative Cycle of Herpes Simplex Virus

Cited by 49 publications

References 63 publications

Herpes simplex virus type-1 induces IFN-α production via Toll-like receptor 9-dependent and -independent pathways

Herpes simplex virus type-1 induces IFN-α production via Toll-like receptor 9-dependent and -independent pathways

Induction of Protective Immunity to Listeria monocytogenes in Neonates

HSV induces an early primary Th1 CD4 T cell response in neonatal mice, but reduced CTL activity at the time of the peak adult response

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