IFN-γ triggers CCR2-independent monocyte entry into the brain during systemic infection by virulent Listeria monocytogenes

2010 ◽  
Vol 24 (6) ◽  
pp. 919-929 ◽  
Author(s):  
Douglas A. Drevets ◽  
Marilyn J. Dillon ◽  
Jennifer E. Schawang ◽  
Julie A. Stoner ◽  
Pieter J.M. Leenen
Keyword(s):  
Listeria Monocytogenes ◽  
Systemic Infection ◽  
Ifn Γ ◽  
The Brain

scholarly journals Induction of IFN-αβ enables Listeria monocytogenes to suppress macrophage activation by IFN-γ

2010 ◽  
Vol 207 (2) ◽  
pp. 327-337 ◽  
Author(s):  
Manira Rayamajhi ◽  
Jessica Humann ◽  
Kristi Penheiter ◽  
Karl Andreasen ◽  
Laurel L. Lenz
Keyword(s):  
Listeria Monocytogenes ◽  
Cross Talk ◽  
Inflammatory Diseases ◽  
Systemic Infection ◽  
Host Susceptibility ◽  
Type I ◽  
Activation Markers ◽  
Beneficial Effects ◽  
Immunological Effects ◽  
Ifn Γ

Production of type I interferon (IFN; IFN-αβ) increases host susceptibility to Listeria monocytogenes, whereas type II IFN (IFN-γ) activates macrophages to resist infection. We show that these opposing immunological effects of IFN-αβ and IFN-γ occur because of cross talk between the respective signaling pathways. We found that cultured macrophages infected with L. monocytogenes were refractory to IFN-γ treatment as a result of down-regulation of the IFN-γ receptor (IFNGR). The soluble factor responsible for these effects was identified as host IFN-αβ. Accordingly, macrophages and dendritic cells (DCs) showed reduced IFNGR1 expression and reduced responsiveness to IFN-γ during systemic infection of IFN-αβ–responsive mice. Furthermore, the increased resistance of mice lacking the IFN-αβ receptor (IFNAR−/−) to L. monocytogenes correlated with increased expression of IFN-γ–dependent activation markers by macrophages and DCs and was reversed by depletion of IFN-γ. Thus, IFN-αβ produced in response to bacterial infection and other stimuli antagonizes the host response to IFN-γ by down-regulating the IFNGR. Such cross talk permits prioritization of IFN-αβ–type immune responses and may contribute to the beneficial effects of IFN-β in treatment of inflammatory diseases such as multiple sclerosis.

scholarly journals Neural Route of Cerebral Listeria monocytogenes Murine Infection: Role of Immune Response Mechanisms in Controling Bacterial Neuroinvasion

2001 ◽  
Vol 69 (2) ◽  
pp. 1093-1100 ◽  
Author(s):  
Yuxuan Jin ◽  
Lone Dons ◽  
Krister Kristensson ◽  
Martı́n E. Rottenberg
Keyword(s):  
Listeria Monocytogenes ◽  
Nk Cells ◽  
Receptor Gene ◽  
Protective Role ◽  
Pathologic Features ◽  
Ifn Γ ◽  
Rag 1 ◽  
The Brain ◽  
Deficient Mice

ABSTRACT The pathologic features of cerebral Listeria monocytogenes infection strongly suggest that besides hematogenous spread, bacteria might also spread via a neural route. We propose that after snout infection of recombination activating gene 1 (RAG-1)-deficient mice, L. monocytogenesspreads to the brain via a neural route. The neural route of invasion is suggested by (i) the immunostaining of L. monocytogenesin the trigeminal ganglia (TG) and brain stem but not in other areas of the brain; (ii) the kinetics of bacterial loads in snout, TG, and brain; and (iii) the increased resistance of mice infected with aplcB bacterial mutant (unable to spread from cell to cell). Gamma interferon (IFN-γ) plays a protective role in neuroinvasion; inducible nitric oxide synthase (iNOS) accounts only partially for the protection, as shown by a comparison of the susceptibilities of IFN-γ receptor (IFN-γR)-deficient, iNOS-deficient, and wild-type mice to snout infection with L. monocytogenes. The dramatically enhanced susceptibility of RAG-1-deficient, IFN-γR gene-deficient mice indicated the overall importance of innate immune cells in the release of protective levels of IFN-γ. The source of IFN-γ appeared to be NK cells, as shown by use ofRAG-1-deficient, γ-chain receptor gene-deficient mice; NK cells played a relevant protective role in neuroinvasion through a perforin-independent mechanism. In vitro evidence indicated that IFN-γ can directly induce bacteriostatic mechanisms in neural tissue.

scholarly journals Comparison of Host Resistance to Primary and Secondary Listeria monocytogenes Infections in Mice by Intranasal and Intravenous Routes

2002 ◽  
Vol 70 (9) ◽  
pp. 4805-4811 ◽  
Author(s):  
Mayuko Mizuki ◽  
Akio Nakane ◽  
Kenji Sekikawa ◽  
Yoh-ich Tagawa ◽  
Yoichiro Iwakura
Keyword(s):  
Listeria Monocytogenes ◽  
Host Resistance ◽  
Systemic Infection ◽  
Intranasal Infection ◽  
Intranasal Immunization ◽  
Host Immune Responses ◽  
Tnf Α ◽  
Ifn Γ ◽  
Factor Α ◽  
Deficient Mice

ABSTRACT There have been no studies on the susceptibility and host immune responses to an intranasal infection with Listeria monocytogenes. In this study, we compared the susceptibilities and cytokine responses between intranasal and intravenous infections with L. monocytogenes in mice. Moreover, we compared efficiency of acquisition of host resistance to L. monocytogenes infection between intranasally and intravenously immunized mice because an intranasal immunization of vaccines is reportedly available for induction of adaptive immunity against various infectious pathogens. The susceptibility to an intranasal infection with L. monocytogenes was markedly lower than that to the intravenous infection. The bacterial growth in the lungs, spleens, and livers was substantially similar between intranasally and intravenously infected mice. Titers of endogenous gamma interferon (IFN-γ) and tumor necrosis factor-α (TNF-α) in the spleens, livers, and lungs were parallel to bacterial numbers in each organ of mice during intranasal infection and intravenous infection. IFN-γ-deficient mice and TNF-α-deficient mice were highly susceptible to intranasal infection as well as intravenous infection. Susceptibilities to intranasal and intravenous L. monocytogenes infection were the same in these cytokine-deficient mice. These results suggest that both IFN-γ and TNF-α play critical roles in host resistance to intranasal L. monocytogenes infection as well as the intravenous infection. Acquisition of host resistance to intravenous and intranasal L. monocytogenes infection was induced in intranasally immunized mice as well as intravenously immunized mice, suggesting that intranasal immunization is effective for prevention of a systemic infection with L. monocytogenes.

scholarly journals Ecklonia cava Attenuates PM2.5-Induced Cognitive Decline through Mitochondrial Activation and Anti-Inflammatory Effect

Marine Drugs ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. 131
Author(s):  
Seon Kyeong Park ◽  
Jin Yong Kang ◽  
Jong Min Kim ◽  
Hyun-Jin Kim ◽  
Ho Jin Heo
Keyword(s):  
Water Extract ◽  
Ecklonia Cava ◽  
Mitochondrial Activity ◽  
Memory Decline ◽  
Mitochondria Membrane Potential ◽  
Mitochondrial Ros ◽  
Ifn Γ ◽  
Related Proteins ◽  
The Brain ◽  
Pro Inflammatory Cytokines

To evaluate the effects of Ecklonia cava (E. cava) on ambient-pollution-induced neurotoxicity, we used a mouse model exposed to particulate matter smaller than 2.5 µm in aerodynamic diameter (PM2.5). The intake of water extract from E. cava (WEE) effectively prevented the learning and memory decline. After a behavioral test, the toll-like receptor (TLR)-4-initiated inflammatory response was confirmed by PM2.5 exposure in the lung and brain tissues, and the WEE was regulated through the inhibition of nuclear factor-kappa B (NF-κB)/inflammasome formation signaling pathway and pro-inflammatory cytokines (IL-6 and IFN-γ). The WEE also effectively improved the PM2.5-induced oxidative damage of the lungs and brain through the inhibition of malondialdehyde (MDA) production and the activation of mitochondrial activity (mitochondrial ROS content, mitochondria membrane potential (MMP), adenosine triphosphate (ATP) content, and mitochondria-mediated apoptotic molecules). In particular, the WEE regulated the cognition-related proteins (a decreased amyloid precursor protein (APP) and p-Tau, and an increased brain-derived neurotrophic factor (BDNF)) associated with PM2.5-induced cognitive dysfunction. Additionally, the WEE prevented the inactivation of acetylcholine (ACh) synthesis and release as a neurotransmitter by regulating the acetylcholinesterase (AChE) activity, choline acetyltransferase (ChAT), and ACh receptor (AChR)-α3 in the brain tissue. The bioactive compounds of the WEE were detected as the polysaccharide (average Mw; 160.13 kDa) and phenolic compounds including 2′-phloroeckol.

scholarly journals Evidence for Differential Roles for NKG2D Receptor Signaling in Innate Host Defense against Coronavirus-Induced Neurological and Liver Disease

2007 ◽  
Vol 82 (6) ◽  
pp. 3021-3030 ◽  
Author(s):  
Kevin B. Walsh ◽  
Melissa B. Lodoen ◽  
Robert A. Edwards ◽  
Lewis L. Lanier ◽  
Thomas E. Lane
Keyword(s):  
Liver Disease ◽  
Immune Responses ◽  
Host Defense ◽  
Nk Cell ◽  
Hepatitis Virus ◽  
Innate Immune ◽  
Liver Pathology ◽  
Innate Immune Responses ◽  
Ifn Γ ◽  
The Brain

ABSTRACT Infection of SCID mice with a recombinant murine coronavirus (mouse hepatitis virus [MHV]) expressing the T-cell chemoattractant CXC chemokine ligand 10 (CXCL10) resulted in increased survival and reduced viral burden within the brain and liver compared to those of mice infected with an isogenic control virus (MHV), supporting an important role for CXCL10 in innate immune responses following viral infection. Enhanced protection in MHV-CXCL10-infected mice correlated with increased gamma interferon (IFN-γ) production by infiltrating natural killer (NK) cells within the brain and reduced liver pathology. To explore the underlying mechanisms associated with protection from disease in MHV-CXCL10-infected mice, the functional contributions of the NK cell-activating receptor NKG2D in host defense were examined. The administration of an NKG2D-blocking antibody to MHV-CXCL10-infected mice did not reduce survival, dampen IFN-γ production in the brain, or affect liver pathology. However, NKG2D neutralization increased viral titers within the liver, suggesting a protective role for NKG2D signaling in this organ. These data indicate that (i) CXCL10 enhances innate immune responses, resulting in protection from MHV-induced neurological and liver disease; (ii) elevated NK cell IFN-γ expression in the brain of MHV-CXCL10-infected mice occurs independently of NKG2D; and (iii) NKG2D signaling promotes antiviral activity within the livers of MHV-infected mice that is not dependent on IFN-γ and tumor necrosis factor alpha secretion.

scholarly journals SARS-CoV-2 infection and persistence throughout the human body and brain

2021 ◽  
Author(s):  
Daniel Chertow ◽  
Sydney Stein ◽  
Sabrina Ramelli ◽  
Alison Grazioli ◽  
Joon-Yong Chung ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Human Body ◽  
Symptom Onset ◽  
Acute Infection ◽  
Systemic Infection ◽  
The Body ◽  
Viral Clearance ◽  
Cell Type ◽  
Cell Type Specificity ◽  
The Brain

Abstract COVID-19 is known to cause multi-organ dysfunction1-3 in acute infection, with prolonged symptoms experienced by some patients, termed Post-Acute Sequelae of SARS-CoV-2 (PASC)4-5. However, the burden of infection outside the respiratory tract and time to viral clearance is not well characterized, particularly in the brain3,6-14. We performed complete autopsies on 44 patients with COVID-19 to map and quantify SARS-CoV-2 distribution, replication, and cell-type specificity across the human body, including brain, from acute infection through over seven months following symptom onset. We show that SARS-CoV-2 is widely distributed, even among patients who died with asymptomatic to mild COVID-19, and that virus replication is present in multiple extrapulmonary tissues early in infection. Further, we detected SARS-CoV-2 RNA in multiple anatomic sites, including regions throughout the brain, for up to 230 days following symptom onset. Despite extensive distribution of SARS-CoV-2 in the body, we observed a paucity of inflammation or direct viral cytopathology outside of the lungs. Our data prove that SARS-CoV-2 causes systemic infection and can persist in the body for months.

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