Increased phagocytosis in the presence of enhanced M2-like macrophage responses correlates with increased primary and latent HSV-1 infection

Jaggi, Ujjaldeep; Yang, Mingjie; Matundan, Harry H.; Hirose, Sachiko; Shah, Prediman K.; Sharifi, Behrooz G.; Ghiasi, Homayon

doi:10.1371/journal.ppat.1008971

Cited by 57 publications

(43 citation statements)

References 58 publications

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“…This reduced phagocytosis could be due to high dose of virus infection (10 pfu/cell) which may have shot down the host immune response leading to lower phagocytosis. Complementing this study, we previously showed that higher levels of M2 macrophages are associated with higher phagocytosis [14].…”

Section: Plos Pathogenssupporting

confidence: 66%

Essential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection

Jaggi

Matundan

et al. 2021

PLoS Pathog

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Ocular HSV-1 infection is a major cause of eye disease and innate and adaptive immunity both play a role in protection and pathology associated with ocular infection. Previously we have shown that M1-type macrophages are the major and earliest infiltrates into the cornea of infected mice. We also showed that HSV-1 infectivity in the presence and absence of M2-macrophages was similar to wild-type (WT) control mice. However, it is not clear whether the absence of M1 macrophages plays a role in protection and disease in HSV-1 infected mice. To explore the role of M1 macrophages in HSV-1 infection, we used mice lacking M1 activation (M1-/- mice). Our results showed that macrophages from M1-/- mice were more susceptible to HSV-1 infection in vitro than were macrophages from WT mice. M1-/- mice were highly susceptible to ocular infection with virulent HSV-1 strain McKrae, while WT mice were refractory to infection. In addition, M1-/- mice had higher virus titers in the eye than did WT mice. Adoptive transfer of M1 macrophages from WT mice to M1-/- mice reduced death and rescued virus replication in the eye of infected mice. Infection of M1-/- mice with avirulent HSV-1 strain KOS also increased ocular virus replication and eye disease but did not affect latency-reactivation seen in WT control mice. Severity of virus replication and eye disease correlated with significantly higher inflammatory responses leading to a cytokine storm in the eyes of M1-/- infected mice that was not seen in WT mice. Thus, for the first time, our study illustrates the importance of M1 macrophages specifically in primary HSV-1 infection, eye disease, and survival but not in latency-reactivation.

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Section: Plos Pathogenssupporting

confidence: 66%

Essential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection

Jaggi

Matundan

et al. 2021

PLoS Pathog

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“…Fas/FasL deficiency promoted the maturation of M1 macrophages which might explain why gld and lpr mice had a better outcome of the infection. It is known that M1 macrophages are refractory to HSV-1 replication, at least in vitro ( 56 ), while M2 macrophages promote viral replication ( 57 ). Activated microglia can control virus replication in the brain by producing inflammatory cytokines and chemokines such as IL-6, IL- 1β, type I interferons (IFN-I), CXCL-10, CCL2 and CCL5, which our data partly confirm.…”

Section: Discussionmentioning

confidence: 99%

Fas/FasL Contributes to HSV-1 Brain Infection and Neuroinflammation

et al. 2021

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The Fas/FasL pathway plays a key role in immune homeostasis and immune surveillance. In the central nervous system (CNS) Fas/FasL is involved in axonal outgrowth and adult neurogenesis. However, little is known about the role of the Fas/FasL pathway in herpes encephalitis. In this study, we used a neuropathogenic clinical strain of herpes simplex virus type 1 (HSV-1) to explore infection-induced inflammation and immune responses in the mouse brain and the role of Fas/FasL in antiviral CNS immunity. HSV-1 CNS infection induced the infiltration of Fas- FasL-bearing monocytes and T cells in the brain and also to an up-regulation of Fas and FasL expression on resident astrocytes and microglia within infected sites. Upon infection, Fas- and FasL-deficient mice (lpr and gld) were partially protected from encephalitis with a decreased morbidity and mortality compared to WT mice. Fas/FasL deficiency promoted cell-mediated immunity within the CNS. Fas receptor stimulation abrogated HSV-1 induced activation and inflammatory reactions in microglia from WT mice, while lack of Fas or FasL led to a more pronounced activation of monocytes and microglia and also to an enhanced differentiation of these cells into a pro-inflammatory M1 phenotype. Furthermore, the specific immune system was more efficient in Fas- and FasL-deficient mice with significantly higher numbers of infiltrating HSV-1-specific cytotoxic T cells in the brain. Our data indicate that the Fas/FasL pathway leads to excessive neuroinflammation during HSV-1 infection, which is associated with a diminished anti-viral response and an excessive neuroinflammation.

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“…These data could be also related to the lower proinflammatory cytokine secretion (TNFα and IL-6) shown in the present study on porcine DAMs. In this sense, we want to highlight that the increased phagocytosis observed in macrophages cultured on pDAM2 could be explained not only by the polarization towards the reparative phenotype of macrophages [ 73 , 74 ] but also by the presence of differentially preserved proteins detected in this pDAM2. Further studies should be addressed in order to explain the relationship of these actin cuffs surrounding C. albicans after macrophage exposure to pDAM2, and the increased phagocytosis previously described.…”

Section: Resultsmentioning

confidence: 99%

“…These data could be also related to the lower proinflammatory cytokine secretion (TNFα and shown in the present study on porcine DAMs. In this sense, we want to highlight that the increased phagocytosis observed in macrophages cultured on pDAM2 could be explained not only by the polarization towards the reparative phenotype of macrophages [73,74] but also by the presence of differentially preserved proteins detected in this pDAM2.…”

Section: Tnfα and Il-6 Production By Raw-2647 Macrophages Cultured On Human Or Porcine Dams After Candida Albicans Interactionmentioning

confidence: 99%

Candida albicans/Macrophage Biointerface on Human and Porcine Decellularized Adipose Matrices

Cicuéndez

Casarrubios

Feito

et al. 2021

JoF

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Macrophages, cells effective in sensing, internalizing and killing Candida albicans, are intertwined with the extracellular matrix (ECM) through different signals, which include the release of specific cytokines. Due to the importance of these interactions, the employment of in vitro models mimicking a fungal infection scenario is essential to evaluate the ECM effects on the macrophage response. In this work, we have analyzed the effects of human and porcine decellularized adipose matrices (DAMs), obtained by either enzymatic or organic solvent treatment, on the macrophage/Candida albicans interface. The present study has allowed us to detect differences on the activation of macrophages cultured on either human- or porcine-derived DAMs, evidencing changes in the macrophage actin cytoskeleton, such as distinct F-actin-rich membrane structures to surround the pathogen. The macrophage morphological changes observed on these four DAMs are key to understand the defense capability of these cells against this fungal pathogen. This work has contributed to the knowledge of the influence that the extracellular matrix and its components can exert on macrophage metabolism, immunocompetence and capacity to respond to the microenvironment in a possible infection scenario.

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Increased phagocytosis in the presence of enhanced M2-like macrophage responses correlates with increased primary and latent HSV-1 infection

Cited by 57 publications

References 58 publications

Essential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection

Essential role of M1 macrophages in blocking cytokine storm and pathology associated with murine HSV-1 infection

Fas/FasL Contributes to HSV-1 Brain Infection and Neuroinflammation

Candida albicans/Macrophage Biointerface on Human and Porcine Decellularized Adipose Matrices

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