CCR2 Plays a Protective Role in Rocio Virus–Induced Encephalitis by Promoting Macrophage Infiltration Into the Brain

Amarilla, Alberto A.; Santos-Júnior, Nilton Nascimento; Figueiredo, Mário Luis Garcia de; Luiz, João; Fumagalli, Marcílio Jorge; Colón, David F.; Lippi, Veronica; Alfonso, Helda Liz; Lima-Júnior, Djalma S.; Trabuco, Amanda Cristina; Spinieli, Richard L; Desiderá, A. C.; Leite–Panissi, Christie Ramos Andrade; Lauretti, Flávio; Mendoza, Silvia Elena Sanchez; Silva, Cleide Lúcia Araújo; Rego, Eduardo Magalhães; Galvão-Lima, Leonardo J.; Bassi, Gabriel Shimizu; Martíns, Sandra L B Penharvel; Manrique, Wilson Gómez; Alves‐Filho, José C.; Cunha, Fernando Q.; Peng, Nias Y. G.; Modhiran, Naphak; Setoh, Yin Xiang; Khromykh, Alexander A.; Figueiredo, Luíz Tadeu Moraes; Aquino, Víctor Hugo

doi:10.1093/infdis/jiz029

Cited by 9 publications

(6 citation statements)

References 45 publications

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“…This is in agreement with the histopathologic damage Rosemberg observed in the same regions of autopsied human brains infected with ROCV [61]. Conversely, the use of CCR2 knockout (Ccr2 −/− ) C57BL/6 mice, demonstrated that CCR2 is required for efficient infiltration of macrophages into the brain, which is associated with a reduction in disease severity and mortality [66].…”

Section: Clinical Presentation and Pathogenesis Of Rocv Infectionsupporting

confidence: 87%

“…Within the genus Flavivirus, ROCV has been classified within the Japanese encephalitis virus (JEV) serogroup, whose members include St. Louis encephalitis virus (SLEV) and Ilhéus virus (ILHV). To date several rodent (BALB/c mice, C57BL/6 mice and golden hamster (Mesocricetus auratus)) studies have been performed, seeking to elucidate ROCV pathogenesis [1,[62][63][64][65][66]. Electron microscopy of ROCV-infected suckling swiss mice brain tissues showed ROCV exclusively located in the lumen of membranous cytoplasmic organelles, principally within hypertrophic Golgi membranes and endo-plasmatic reticulum, intracytoplasmic vesicles, and the nuclear envelope [1], observations commonly seen in neurotropic flavivirus infections [67][68][69].…”

Section: Clinical Presentation and Pathogenesis Of Rocv Infectionmentioning

confidence: 99%

“…Using CCR5 and MIP-1a knockout mice they demonstrated increased survival rates compared to wild-type (wt) ROCV-infected animals, as well as significantly reduced inflammation and viral loads in the brains of the knockout mice, suggesting CCR5/MIP-1a mediates lymphocyte recruitment in the brain leading to disease severity [64]. Recently, Amarilla et al [66] investigated the role of monocytes in the ROCV-induced inflammatory response in the brain. Migration of monocytes into the brain is heavily dependent on the interaction between the C-C Motif Chemokine Ligand 2 (CCL2) and its receptor C-C Motif Chemokine Receptor 2 (CCR2).…”

Section: Clinical Presentation and Pathogenesis Of Rocv Infectionmentioning

confidence: 99%

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Rocio Virus: An Updated View on an Elusive Flavivirus

Saivish

Costa

Silva

et al. 2021

Viruses

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Rocio virus (ROCV) is a mosquito-borne flavivirus and human pathogen. The virus is indigenous to Brazil and was first detected in 1975 in the Sao Paulo State, and over a period of two years was responsible for several epidemics of meningoencephalitis in coastal communities leading to over 100 deaths. The vast majority of ROCV infections are believed to be subclinical and clinical manifestations can range from uncomplicated fever to fatal meningoencephalitis. Birds are the natural reservoir and amplification hosts and ROCV is maintained in nature in a mosquito-bird-mosquito transmission cycle, primarily involving Psorophora ferox mosquitoes. While ROCV has remained mostly undetected since 1976, in 2011 it re-emerged in Goiás State causing a limited outbreak. Control of ROCV outbreaks depends on sustainable vector control measures and public education. To date there is no specific treatment or licensed vaccine available. Here we provide an overview of the ecology, transmission cycles, epidemiology, pathogenesis, and treatment options, aiming to improve our ability to understand, predict, and ideally avert further ROCV emergence.

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Section: Clinical Presentation and Pathogenesis Of Rocv Infectionsupporting

confidence: 87%

Section: Clinical Presentation and Pathogenesis Of Rocv Infectionmentioning

confidence: 99%

Section: Clinical Presentation and Pathogenesis Of Rocv Infectionmentioning

confidence: 99%

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Rocio Virus: An Updated View on an Elusive Flavivirus

Saivish

Costa

Silva

et al. 2021

Viruses

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“…Brain-associated macrophages were defined as live CD45 hi CD11b + Ly6C À (Figure 3a), 14,15 and comprised ~25% of the peripheral leukocyte population in the brains of sham-operated mice (Figure 3b). In contrast to our findings in neutrophils and monocytes, we found that the proportions of macrophages in both the CL and IL hemispheres of tMCAO mice, and the IL hemisphere of pMCAO mice, were decreased compared with corresponding sham-operated counterparts (tMCAO CL: 16.9% AE 2.2% versus sham CL: 27.1% AE 1.9%, P = 0.0016; tMCAO IL: 16.6% AE 2.4% versus sham IL: 27.8% AE 1.5%, P = 0.0005; pMCAO IL: 18.8% AE 2.1% versus sham IL, P = 0.0017; Figure 3b).…”

Section: Macrophage Heterogeneity At 24 H After Strokementioning

confidence: 99%

Brain‐associated innate leukocytes display diverse inflammatory states following experimental stroke

et al. 2022

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Previous studies investigating innate leukocyte recruitment into the brain after cerebral ischemia have shown conflicting results. Using distinct cell surface and intracellular markers, the current study evaluated the contributions of innate immune cells to the poststroke brain following 1‐h middle cerebral artery occlusion (tMCAO) or permanent MCAO (pMCAO), and assessed whether these cells ascribed to an inflammatory state. Moreover, we examined whether there is evidence for leukocyte infiltration into the contralateral (CL) hemisphere despite the absence of stroke infarct. We observed the recruitment of peripheral neutrophils, monocytes and macrophages into the hemisphere ipsilateral (IL) to the ischemic brain infarct at 24 and 96 h following both tMCAO and pMCAO. In addition, we found evidence of increased leukocyte recruitment to the CL hemisphere but to a lesser extent than the IL hemisphere after stroke. Robust production of intracellular cytokines in the innate immune cell types examined was most evident at 24 h after pMCAO. Specifically, brain‐associated neutrophils, monocytes and macrophages demonstrated stroke‐induced production of tumor necrosis factor‐α (TNF‐α) and interleukin (IL)‐1β, while only monocytes and macrophages exhibit a significant expression of arginase 1 (Arg1) after stroke. At 96 h after stroke, brain‐resident microglia demonstrated production of TNF‐α and IL‐1β following both tMCAO and pMCAO. At this later timepoint, neutrophils displayed TNF‐α production and brain‐associated macrophages exhibited elevation of IL‐1β and Arg1 after tMCAO. Further, pMCAO induced significant expression of Arg1 and IL‐1β in monocytes and macrophages at 96 h, respectively. These results revealed that brain‐associated innate immune cells display various stroke‐induced inflammatory states that are dependent on the experimental stroke setting.

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“…Rocio virus (ROCV) is a potentially emerging neurotropic flavivirus in Brazil; however, because relatively little is known about the biology of this virus, technologies for its detection are limited (3)(4)(5). In 1975, ROCV was found to be related to the causative agent of a fatal outbreak of human encephalitis in Brazil; the case-fatality rate was 13%, and neurologic sequelae affected 20% of patients (5).…”

mentioning

confidence: 99%