IFN-α-driven CCL2 production recruits inflammatory monocytes to infection site in mice

Conrady, Christopher D.; Zheng, Min; Mandal, Nawajes A.; Rooijen, Nico van; Carr, Daniel J.J.

doi:10.1038/mi.2012.46

Cited by 91 publications

(112 citation statements)

References 51 publications

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“…27 Taken together, such findings provide evidence to suggest NK cells and activated monocytes/macrophages are critical for viral clearance during acute HSV-1 infection.…”

Section: Discussionmentioning

confidence: 71%

CXCL1-Deficient Mice Are Highly Sensitive toPseudomonas aeruginosabut Not Herpes Simplex Virus Type 1 Corneal Infection

Bryant-Hudson

Carr²

2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE.To determine the role of the chemokine CXCL1 on leukocyte recruitment, cytokine production and host resistance during HSV-1 and Pseudomonas aeruginosa infection.METHODS. Viral titer and bacterial load were compared following infection of wild-type (WT) and CXCL1 À/À mice. Corneal leukocyte recruitment was determined using flow cytometry. Cytokine levels were assessed by luminex-based suspension arrays. Hematoxylin and eosin (H&E) staining, confocal microscopy, and optical coherence tomography (OCT) were used to visualize leukocyte recruitment and corneal thickening. RESULTS. HSV-1-infected WT and CXCL1À/À mice possessed similar viral titers in the cornea during late acute infection. Flow cytometry analysis detected similar leukocyte levels in the cornea following infection as well. By comparison, there was a significant increase in P. aeruginosa recovered from CXCL1 À/À corneas as compared with WT mice. Imaging analysis and histochemical staining revealed impaired leukocyte recruitment to the central cornea and earlier corneal thickening in CXCL1 À/À mice. IFN-c, CCL2, and CCL5 protein levels were similar between WT and CXCL1 À/À corneas following HSV-1 or P. aeruginosa infection. However, CXCL2 levels were significantly reduced in the CXCL1 À/À corneas following either infection.CONCLUSIONS. The absence of CXCL1 and CXCL2 expression significantly impairs the ability of the host to control P. aeruginosa replication through the recruitment of leukocytes to the central cornea. In contrast, CXCL1, CXCL2, and the cells they recruit, are not required for HSV-1 clearance during acute infection. (Invest Ophthalmol Vis Sci. 2012;53:6785-6792)

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“…27 Taken together, such findings provide evidence to suggest NK cells and activated monocytes/macrophages are critical for viral clearance during acute HSV-1 infection.…”

Section: Discussionmentioning

confidence: 71%

CXCL1-Deficient Mice Are Highly Sensitive toPseudomonas aeruginosabut Not Herpes Simplex Virus Type 1 Corneal Infection

Bryant-Hudson

Carr²

2012

Invest. Ophthalmol. Vis. Sci.

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“…Taken together, these results indicate that the absence of CXCL10 decreases the primary influx of neutrophils, which have been shown to participate in HSV-1 clearance directly or indirectly by activating other inflammatory cells, such as monocytes (1,(4)(5)(6)(7)(8).…”

Section: Absence Of Cxcl10 Decreases the Primary Neutrophil Influx Dumentioning

confidence: 65%

“…The primary neutrophil influx reaches a peak at 2 to 3 days p.i., declines to a basal level at 5 days p.i., and participates in virus clearance directly or indirectly by activating other inflammatory cells, such as monocytes (1,(4)(5)(6)(7)(8). The secondary neutrophil influx is more intense, begins at 8 to 9 days p.i., and reaches a peak at about 2 to 3 weeks p.i.…”

mentioning

confidence: 99%

Absence of CXCL10 Aggravates Herpes Stromal Keratitis with Reduced Primary Neutrophil Influx in Mice

Shen

Wang

Yeh

et al. 2013

J Virol

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“…ϩ Gr-1 ϩ monocytes, which are associated with acute viral clearance (47). Neutrophil (F4/80 Ϫ Gr-1 ϩ ) infiltration was appreciably limited in both vaccinated groups compared to that in naive animals (Fig.…”

Section: Resultsmentioning

confidence: 99%

A Highly Efficacious Herpes Simplex Virus 1 Vaccine Blocks Viral Pathogenesis and Prevents Corneal Immunopathology via Humoral Immunity

Royer

Gurung

Jinkins

et al. 2016

J Virol

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Correlates of immunologic protection requisite for an efficacious herpes simplex virus 1 (HSV-1) vaccine remain unclear with respect to viral pathogenesis and clinical disease. In the present study, mice were vaccinated with a novel avirulent, live attenuated virus (0⌬NLS) or an adjuvanted glycoprotein D subunit (gD-2) similar to that used in several human clinical trials. Mice vaccinated with 0⌬NLS showed superior protection against early viral replication, neuroinvasion, latency, and mortality compared to that of gD-2-vaccinated or naive mice following ocular challenge with a neurovirulent clinical isolate of HSV-1. Moreover, 0⌬NLS-vaccinated mice exhibited protection against ocular immunopathology and maintained corneal mechanosensory function. Vaccinated mice also showed suppressed T cell activation in the draining lymph nodes following challenge. Vaccine efficacy correlated with serum neutralizing antibody titers. Humoral immunity was identified as the correlate of protection against corneal neovascularization, HSV-1 shedding, and latency through passive immunization. Overall, 0⌬NLS affords remarkable protection against HSV-1-associated ocular sequelae by impeding viral replication, dissemination, and establishment of latency. IMPORTANCEHSV-1 manifests in a variety of clinical presentations ranging from a rather benign "cold sore" to more severe forms of infection, including necrotizing stromal keratitis and herpes simplex encephalitis. The present study was undertaken to evaluate a novel vaccine to ocular HSV-1 infection not only for resistance to viral replication and spread but also for maintenance of the visual axis. The results underscore the necessity to reconsider strategies that utilize attenuated live virus as opposed to subunit vaccines against ocular HSV-1 infection. Herpes simplex virus 1 (HSV-1) is a highly successful human pathogen that results in approximately 40,000 new cases of severe visual impairment each year (1). In such cases, the immune response to the pathogen inadvertently mediates corneal pathology. Moreover, the morbidity associated with ocular infection results from episodic viral recrudescence (2, 3). This etiology is dependent upon reactivation of HSV-1 from latently infected neurons within the trigeminal ganglion (TG), which innervates the cornea and orofacial mucosae. Although gamma interferon (IFN-␥) and other cytokines secreted by T cells and other cornearesident cells facilitate viral clearance in the cornea, these soluble factors also recruit neutrophils and activate macrophages replete with proteases that instigate extracellular matrix remodeling and scar formation, thereby compromising visual acuity (4-10). Furthermore, protracted inflammatory responses sustained beyond clearance of the virus contribute to corneal neovascularization (1, 11). Consequently, developing HSV vaccines that elicit robust protection against infection without enhancing the risk for corneal immunopathology is an important clinical matter as no sanctioned HSV vaccine clinical trials to dat...

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IFN-α-driven CCL2 production recruits inflammatory monocytes to infection site in mice

Cited by 91 publications

References 51 publications

CXCL1-Deficient Mice Are Highly Sensitive toPseudomonas aeruginosabut Not Herpes Simplex Virus Type 1 Corneal Infection

CXCL1-Deficient Mice Are Highly Sensitive toPseudomonas aeruginosabut Not Herpes Simplex Virus Type 1 Corneal Infection

Absence of CXCL10 Aggravates Herpes Stromal Keratitis with Reduced Primary Neutrophil Influx in Mice

A Highly Efficacious Herpes Simplex Virus 1 Vaccine Blocks Viral Pathogenesis and Prevents Corneal Immunopathology via Humoral Immunity

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