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1.
Int J Rheum Dis ; 24(11): 1427-1439, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34633142

ABSTRACT

AIM: To review the clinical features of systemic lupus erythematosus (SLE) complicated by central nervous system (CNS) infection due to Listeria monocytogenes. METHOD: A patient with SLE receiving high-dose glucocorticoids combined with cyclophosphamide who developed multiple brain abscesses due to Listeria infection is described. The case is compared with known cases in a literature review. RESULTS: A review of the literature showed that CNS infections are rare bacterial complications of SLE, but they can be a significant cause of mortality, especially those due to L. monocytogenes. The most significant risk factor for listerial meningitis is a prior history of receiving immunosuppressive therapy. At-risk patients should avoid unpasteurized milk and soft cheeses along with deli-style, ready-to-eat prepared meats, particularly poultry products. The case we report is the fifth SLE patient with multiple brain abscesses due to L. monocytogenes, and the first to be discharged with no sequelae. Timely and accurate identification and treatment of CNS infections and neuropsychiatric lupus are very important for favorable disease prognosis. CONCLUSION: Repeated blood culture is helpful for early diagnosis, and empirical anti-infective treatment that covers L. monocytogenes is recommended for SLE patients with risk factors when CNS infection occurs. A comprehensive assessment might be helpful to distinguish CNS infections from neuropsychiatric SLE. For severe infection, the dosage of steroids does not need to be reduced immediately but can be gradually adjusted based on the results of a comprehensive evaluation of the disease.


Subject(s)
Brain Abscess/microbiology , Cyclophosphamide/adverse effects , Glucocorticoids/adverse effects , Immunosuppressive Agents/adverse effects , Listeria monocytogenes/pathogenicity , Lupus Erythematosus, Systemic/drug therapy , Meningitis, Listeria/microbiology , Anti-Bacterial Agents/therapeutic use , Brain Abscess/diagnosis , Brain Abscess/drug therapy , Brain Abscess/immunology , Female , Humans , Immunocompromised Host , Listeria monocytogenes/immunology , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/immunology , Meningitis, Listeria/diagnosis , Meningitis, Listeria/drug therapy , Meningitis, Listeria/immunology , Middle Aged , Risk Factors , Treatment Outcome
2.
Int Immunopharmacol ; 97: 107695, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33962227

ABSTRACT

Staphylococcus aureus induced brain abscess is a critical health concern throughout the developing world. The conventional surgical intervention could not regulate the abscess-induced brain inflammation. Thus further study over the alternative therapeutic strategy for treating a brain abscess is of high priority. The resident glial cells recognize the invading S. aureus by their cell surface Toll-like receptor-2 (TLR-2). Glucocorticoid receptor (GR) was known for its immunosuppressive effects. In this study, an attempt had been taken to utilize the functional relationship or cross-talking between TLR-2 and GR during the pathogenesis of brain abscesses. Here, the combination of an antibiotic (i.e. ciprofloxacin) and dexamethasone was used to regulate the brain inflammation either in TLR-2 or GR blocking condition. We were also interested to figure out the possible impact of alternative therapy on behavioral impairments. The results indicated that combination treatment during TLR-2 blockade significantly reduced the bacterial burden and abscess area score in the infected brain. However, marked improvements were observed in anxiety, depression-like behavior, and motor co-ordination. The combination treatment after TLR-2 blocking effectively scavenged free radicals (H2O2, superoxide anion, and NO) through modulating antioxidant enzyme activities that ultimately control S. aureus induced glial reactivity possibly via up-regulating GR expression. The exogenous dexamethasone might regulate the GR expression in the brain by increasing the corticosterone concentration and the GC-GR mediated signaling. Therefore, this in-vivo study demonstrates the possible regulatory mechanism of bacterial brain abscess that involved TLR-2 and GR as a part of neuroendocrine-immune interaction.


Subject(s)
Brain Abscess/drug therapy , Ciprofloxacin/pharmacology , Dexamethasone/pharmacology , Neuroinflammatory Diseases/drug therapy , Staphylococcal Infections/drug therapy , Animals , Behavior, Animal/drug effects , Brain Abscess/complications , Brain Abscess/immunology , Brain Abscess/microbiology , Ciprofloxacin/therapeutic use , Dexamethasone/therapeutic use , Disease Models, Animal , Drug Therapy, Combination , Humans , Male , Mice , Neuroinflammatory Diseases/diagnosis , Neuroinflammatory Diseases/immunology , Neuroinflammatory Diseases/microbiology , Neurosecretory Systems/drug effects , Neurosecretory Systems/immunology , Receptors, Glucocorticoid/metabolism , Signal Transduction/drug effects , Signal Transduction/immunology , Staphylococcal Infections/complications , Staphylococcal Infections/immunology , Staphylococcal Infections/microbiology , Staphylococcus aureus/drug effects , Staphylococcus aureus/immunology , Toll-Like Receptor 2/metabolism
3.
J Clin Res Pediatr Endocrinol ; 13(3): 358-361, 2021 08 23.
Article in English | MEDLINE | ID: mdl-32840095

ABSTRACT

Brain abscess formation is extremely rare in patients with osteopetrosis. Herein, we report a case of viridans streptococci brain abscess in an immunocompromised child diagnosed with osteopetrosis. The patient presented with a sudden change in mental status and convulsions. Radiological evaluation revealed a temporal lobe brain abscess, and intravenous antibiotherapy was started immediately. The patient underwent abscess drainage, and laboratory investigation of pus material revealed viridans streptococci.


Subject(s)
Agammaglobulinemia/immunology , Brain Abscess/microbiology , Central Nervous System Bacterial Infections/microbiology , Immunocompromised Host , Osteopetrosis/immunology , Streptococcal Infections/microbiology , Viridans Streptococci/isolation & purification , Adolescent , Agammaglobulinemia/diagnosis , Agammaglobulinemia/genetics , Anti-Bacterial Agents/therapeutic use , Brain Abscess/diagnosis , Brain Abscess/immunology , Brain Abscess/therapy , Central Nervous System Bacterial Infections/diagnosis , Central Nervous System Bacterial Infections/immunology , Central Nervous System Bacterial Infections/therapy , Drainage , Humans , Male , Osteopetrosis/diagnosis , Osteopetrosis/genetics , Risk Factors , Streptococcal Infections/diagnosis , Streptococcal Infections/immunology , Streptococcal Infections/therapy , Treatment Outcome , Viridans Streptococci/drug effects
4.
Biomed Res Int ; 2019: 6076571, 2019.
Article in English | MEDLINE | ID: mdl-31080825

ABSTRACT

Cerebral involvement especially brain abscess is life-threatening complication and major cause of death during Scedosporium apiospermum infection. However, little is known about pathogenesis of brain oedema associated with abscess in scedosporiosis. Experimental scedosporiosis was conducted in BALB/cMlac mice to characterize the presence of brain oedema, its type, and its related mechanisms focusing on aquaporin (AQP)-4, nuclear factor erythroid-2 related factor (Nrf-2), and tumor necrotic factor (TNF)-α. The results revealed that S. apiospermum infection induced severe inflammatory environment relevant to TNF-α expression and cytogenic oedema-associated brain abscess predominately in cerebrum of immunocompromised mice without voriconazole treatment reflecting to downregulation of AQP-4 in neighboring abscess areas and oedematous blood vessels. Downregulation of Nrf-2 in neuronal cells and myelin degeneration were significantly observed in nontreated mice. In summary, oxidative stress, severe inflammatory response, and space-occupying mass from abscess formation inducing tissue hypoxia might be the postulate causes of oedema induced by scedosporiosis.


Subject(s)
Aquaporin 4/metabolism , Brain Abscess/immunology , Brain Abscess/metabolism , Brain Edema/metabolism , Mycoses/immunology , NF-E2-Related Factor 2/metabolism , Scedosporium/pathogenicity , Animals , Brain/blood supply , Brain/pathology , Brain Abscess/pathology , Down-Regulation , Female , Hypoxia , Immunocompromised Host/drug effects , Mice , Mice, Inbred BALB C , Mycoses/pathology , Myelin Sheath , Oxidative Stress , Tumor Necrosis Factor-alpha/metabolism , Voriconazole/pharmacology
6.
Rheumatol Int ; 38(12): 2323-2328, 2018 12.
Article in English | MEDLINE | ID: mdl-30374688

ABSTRACT

Central nervous system infections, which are rarely seen in systemic lupus erythematosus (SLE), have considerably high mortality but they are difficult to distinguish from neuropsychiatric manifestation of lupus. This article reports the case of a patient with SLE with brain abscess which developed during immunosuppressive therapy for lupus nephritis. The patient completely recovered without neurological sequelae by open surgical drainage and 12-week antibiotic therapy. It is recommended that CNS infections must be excluded in patients with SLE, particularly who are receiving immunosuppressive therapy.


Subject(s)
Brain Abscess/microbiology , Central Nervous System Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/microbiology , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Lupus Erythematosus, Systemic/drug therapy , Lupus Nephritis/drug therapy , Micrococcus luteus/isolation & purification , Opportunistic Infections/microbiology , Adult , Anti-Bacterial Agents/administration & dosage , Bacteriological Techniques , Brain Abscess/diagnosis , Brain Abscess/immunology , Brain Abscess/therapy , Central Nervous System Bacterial Infections/diagnosis , Central Nervous System Bacterial Infections/immunology , Central Nervous System Bacterial Infections/therapy , Diagnosis, Differential , Drainage , Female , Gram-Positive Bacterial Infections/diagnosis , Gram-Positive Bacterial Infections/immunology , Gram-Positive Bacterial Infections/therapy , Humans , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/immunology , Lupus Nephritis/diagnosis , Lupus Nephritis/immunology , Lupus Vasculitis, Central Nervous System/diagnosis , Lupus Vasculitis, Central Nervous System/immunology , Magnetic Resonance Imaging , Micrococcus luteus/drug effects , Micrococcus luteus/immunology , Opportunistic Infections/diagnosis , Opportunistic Infections/immunology , Opportunistic Infections/therapy , Predictive Value of Tests , Treatment Outcome
7.
J Clin Neurosci ; 53: 135-139, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29716805

ABSTRACT

Although brain abscess is a fatal neurological infection, the studies in Thailand are quite limited and outdate. This study aims to identify predictors of mortality among patients with brain abscess in Thailand. Patients with a diagnosis of brain abscess admitted to Songklanagarind Hospital, a referral tertiary care hospital in southern Thailand, between 2002 and 2017 were enrolled into this retrospective case control study. Demographic data, neurological status, clinical presentations, predisposing factors, microbiological profiles, neuroimaging findings, treatments, and outcomes were collected from electronic medical records. Predictors of death outcome were analyzed by univariate and multivariate logistic regression analysis. Among eighty-one patients enrolled into the study, forty-seven patients (58.0%) were male and 34 patients (42.0%) were female. The overall mean age (±SD) was 47.68 (±16.92) years old. The major predisposing factors of brain abscess were an immunocompromised state (42.0%) and the extension of a paracranial infections (24.7%). The common clinical presentations included headache (61.7%), fever (50.6%), and hemiplegia (34.6%). Eleven patients (13.6%) were dead at hospital discharge. The independent factor associated with death outcome identified by multivariate analysis was confusion (odds ratio 7.67, 95% CI 1.95-30.14; p = 0.003). In summary, the current study shows that an immunocompromised state is a significant predisposing factor of brain abscess. The independent factor associated with death outcome was confusion which was correlated with septic encephalopathy.


Subject(s)
Brain Abscess/etiology , Brain Abscess/mortality , Adult , Aged , Brain Abscess/immunology , Case-Control Studies , Female , Humans , Immunocompromised Host , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Retrospective Studies , Thailand/epidemiology , Young Adult
8.
Exp Clin Transplant ; 16 Suppl 1(Suppl 1): 179-182, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29528023

ABSTRACT

Neurologic complications after solid-organ transplant reveal a great spectrum of pathologies. Intracranial hemorrhages, cerebral ischemic lesions, infarctions, lymphoproliferative disorders, and infections, including aspergillosis, have been observed after liver transplant. Fungi constitute nearly 5% of all central nervous system infections, mainly occurring in immunocompromised patients. The most common causative agent is Aspergillus species. It presents either as maxillary sinusitis or pulmonary infection. Brain involvement of Aspergillus carries a high rate of mortality. Aspergillosis presents in the forms of meningitis, mycotic aneurysms, infarctions, and mass lesions. Aspergillosis does not have a specific radiologic appearance. Parenchymal aspergillosis has heterogenous signal intensity (hypointense on T1-weighted and hyperintense on T2-weighted images). Here, we present 3 patients who underwent solid-organ transplant and developed central nervous system aspergillosis. Different modalities of neurosurgical intervention were performed in combination with chemotherapy as part of their fungal therapy.


Subject(s)
Brain Abscess/microbiology , Hydrocephalus/microbiology , Kidney Transplantation/adverse effects , Liver Transplantation/adverse effects , Neuroaspergillosis/microbiology , Opportunistic Infections/microbiology , Adult , Antifungal Agents/therapeutic use , Brain Abscess/diagnostic imaging , Brain Abscess/drug therapy , Brain Abscess/immunology , Female , Humans , Hydrocephalus/diagnostic imaging , Hydrocephalus/drug therapy , Hydrocephalus/immunology , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Magnetic Resonance Imaging , Male , Middle Aged , Neuroaspergillosis/diagnostic imaging , Neuroaspergillosis/drug therapy , Neuroaspergillosis/immunology , Opportunistic Infections/diagnostic imaging , Opportunistic Infections/drug therapy , Opportunistic Infections/immunology , Tomography, X-Ray Computed , Treatment Outcome
9.
Ugeskr Laeger ; 179(23)2017 Jun 05.
Article in Danish | MEDLINE | ID: mdl-28606302

ABSTRACT

Nocardiosis is primarily an opportunistic infection caused by aerobic Gram-positive bacteria of the genus Nocardia. In this case report we describe a male patient who previously received a kidney transplant and was admitted to hospital with chills, headache and pain in the neck and left eye, tremor and coordination problems. A magnetic resonance scan of the brain showed multiple abscesses, and blood culture was positive for Nocardia farcinica. Nocardiosis of the central nervous system is a rare, but serious differential diagnosis in immunosuppressed patients with signs of high intracranial pressure.


Subject(s)
Brain Abscess/microbiology , Nocardia Infections , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Brain Abscess/diagnostic imaging , Brain Abscess/drug therapy , Brain Abscess/immunology , Denmark , Humans , Immunocompromised Host , Kidney Transplantation , Magnetic Resonance Imaging , Male , Middle Aged , Nocardia/isolation & purification , Nocardia Infections/complications , Nocardia Infections/diagnosis , Nocardia Infections/drug therapy , Nocardia Infections/immunology , Pakistan/ethnology
10.
J Infect Public Health ; 10(5): 674-677, 2017.
Article in English | MEDLINE | ID: mdl-28545899

ABSTRACT

Brain abscesses due to Enterobacteriaceae in immune-competent children are rare, and those due to Enterobacter cloacae are even rarer. We report an interesting case of community-acquired E. cloacae neuroinfection resulting in multiple brain abscesses in a young child with no underlying risk-factors. A 10 year-old-boy presented with low-grade fever, headache, neck pain and progressive deterioration of sensorium. On examination, he was conscious but drowsy with photophobia, normal fundii, meningeal signs, mild hypertonia, brisk muscle stretch reflexes and extensor plantar responses. Magnetic resonance imaging of brain showed bilateral, multiple pyogenic abscesses. Culture of the abscess material aspirated at the time of surgical drainage showed growth of E. cloacae. He received intravenous imipenem for 18 weeks guided by clinical and radiological response. A pragmatic approach combining early surgical drainage, targeted antimicrobial therapy and patient-tailored duration based on the clinico-radiological response is needed in such difficult cases.


Subject(s)
Brain Abscess/microbiology , Enterobacter cloacae , Enterobacteriaceae Infections/microbiology , Brain/pathology , Brain Abscess/diagnostic imaging , Brain Abscess/immunology , Child , Community-Acquired Infections/diagnostic imaging , Community-Acquired Infections/microbiology , Enterobacteriaceae Infections/diagnostic imaging , Enterobacteriaceae Infections/immunology , Enterobacteriaceae Infections/physiopathology , Humans , Magnetic Resonance Imaging , Male
11.
Exp Clin Transplant ; 15(1): 110-113, 2017 Feb.
Article in English | MEDLINE | ID: mdl-26375027

ABSTRACT

Invasive aspergillosis is one of the most important and fatal complications after liver transplant, especially in patients with involvement of the central nervous system. We present a case of a patient who developed cerebral and pulmonary aspergillosis, coinfected with cytomegalovirus, after liver transplant for toxic fulminant hepatitis. The patient was treated successfully with neurosurgical intervention and voriconazole. Voriconazole is considered more effective in cerebral aspergillosis than other anti-fungal agents due to the greater penetration into central nervous system and higher cerebrospinal fluid and brain tissue levels.


Subject(s)
Antifungal Agents/therapeutic use , Brain Abscess/therapy , Chemical and Drug Induced Liver Injury/surgery , Cytomegalovirus Infections/therapy , Invasive Pulmonary Aspergillosis/therapy , Liver Transplantation/adverse effects , Lung Abscess/therapy , Mushroom Poisoning/complications , Neuroaspergillosis/therapy , Neurosurgical Procedures , Opportunistic Infections/therapy , Voriconazole/therapeutic use , Biopsy , Brain Abscess/immunology , Brain Abscess/microbiology , Brain Abscess/virology , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/etiology , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/virology , Female , Humans , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Invasive Pulmonary Aspergillosis/immunology , Invasive Pulmonary Aspergillosis/microbiology , Lung Abscess/immunology , Lung Abscess/microbiology , Magnetic Resonance Imaging , Middle Aged , Mushroom Poisoning/diagnosis , Neuroaspergillosis/immunology , Neuroaspergillosis/microbiology , Opportunistic Infections/immunology , Opportunistic Infections/microbiology , Opportunistic Infections/virology , Tomography, X-Ray Computed , Treatment Outcome
15.
Exp Clin Transplant ; 13 Suppl 3: 77-80, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26640919

ABSTRACT

Fungal brain abscesses are a rare but serious complication in transplant recipients. Phialemonium organisms are rare causes of invasive mold infections. Here, we present the first case of a renal transplant recipient with multiple brain abscesses caused by Phialemonium infection A. A 51-year-old female kidney transplant recipient was admitted with pneumonia of an unknown cause and treated with empiric intravenous antibiotics. Her treatment was uneventful, and she was discharged 1010 days later. After 5 days, she was readmitted with fever, cerebral palsy, and speech disorder. The patient had undergone living-donor renal transplant 7 months earlier. A cranial computed tomography and magnetic resonance imaging were performed for a possible cerebrovascular pathology. The magnetic resonance imaging scan showed multiple brain abscesses located at the left parietal, frontal and occipital lobes; right parietal and occipital lobes; right basal ganglia; and left cerebellum. The patient received meropenem, linezolid, sulfamethoxazole and trimethoprim, and AmBisome for probable pathogenic infection, and immunosuppressive agents dosage was reduced increasingly immunosuppressed. We identified Phialemonium in cerebrospinal fluid culture. The patient received voriconazole 200 mg twice daily. Lesions could not be drained due to lack of capsula formation. The patient died on the 30th day of antifungal therapy. Phialemonium organisms, although a rare cause of fungal infections, are associated with a high mortality rate in immunocompromised patients. To our knowledge, this is the first case report in the literature describing multiple brain abscesses due to Phialemonium in a transplant recipient. Clinicians recipient should be alert about these rare opportunistic fungi in the differential diagnosis of brain abscess, and bronchoscopy and bronchoalveolar lavage are recommended for transplant patients when they are admitted with pneumonia exclude fungal infections.


Subject(s)
Ascomycota/isolation & purification , Brain Abscess/microbiology , Central Nervous System Fungal Infections/microbiology , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Opportunistic Infections/microbiology , Antifungal Agents/therapeutic use , Brain Abscess/diagnosis , Brain Abscess/immunology , Central Nervous System Fungal Infections/diagnosis , Central Nervous System Fungal Infections/immunology , Fatal Outcome , Female , Humans , Magnetic Resonance Imaging , Middle Aged , Opportunistic Infections/diagnosis , Opportunistic Infections/immunology , Time Factors , Tomography, X-Ray Computed , Treatment Failure
16.
J Pediatr Hematol Oncol ; 37(7): 568-9, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26274034

ABSTRACT

A 5-year-old boy with standard-risk B-cell acute lymphoblastic anemia developed fever during induction chemotherapy. The patient had no neurological symptoms. Blood cultures grew Bacillus cereus and neuroimaging studies demonstrated a cerebral abscess. Imaging changes resolved after completion of antibiotics. Bacillus cereus bacteremia is increasingly implicated as the cause of life-threatening infections, including cerebral abscesses, in compromised patients. Positive blood cultures for this organism should prompt neuroimaging and consideration of cerebrospinal fluid sampling, as well as catheter removal. Given the worse outcome with central nervous system involvement, there is a need for increased awareness and early diagnosis, particularly in immunocompromised individuals.


Subject(s)
Brain Abscess/diagnosis , Brain Abscess/microbiology , Gram-Positive Bacterial Infections/diagnosis , Gram-Positive Bacterial Infections/etiology , Induction Chemotherapy/adverse effects , Leukemia, B-Cell/drug therapy , Bacillus cereus , Brain Abscess/immunology , Child, Preschool , Gram-Positive Bacterial Infections/immunology , Humans , Immunocompromised Host , Magnetic Resonance Imaging , Male
18.
Neuroradiol J ; 27(3): 334-8, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24976201

ABSTRACT

We describe the case of a 62-year-old man, who presented with a new onset of focal seizures of his right leg. There were no other clinical symptoms, and laboratory results were normal. Brain magnetic resonance imaging revealed multiple lesions, two supratentorial lesions were ring-enhancing. The brain biopsy tissue showed Histoplasma capsulatum abscesses. He improved on treatment with Amphotericin B. This case is reported since cerebral ring-enhancing lesions are rarely associated with histoplasmosis, which is also rare in an immunocompetent individual. We review the literature and discuss the radiologic and pathologic findings of this case compared with previous reports.


Subject(s)
Brain Abscess/immunology , Brain Abscess/pathology , Encephalitis/complications , Encephalitis/immunology , Histoplasmosis/immunology , Histoplasmosis/pathology , Immunocompetence/immunology , Brain/pathology , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged
19.
J Neurochem ; 129(4): 704-11, 2014 May.
Article in English | MEDLINE | ID: mdl-24484406

ABSTRACT

Interleukin-1ß (IL-1ß) is essential for eliciting protective immunity during the acute phase of Staphylococcus aureus (S. aureus) infection in the central nervous system (CNS). We previously demonstrated that microglial IL-1ß production in response to live S. aureus is mediated through the Nod-like receptor protein 3 (NLRP3) inflammasome, including the adapter protein ASC (apoptosis-associated speck-like protein containing a caspase-1 recruitment domain), and pro-caspase 1. Here, we utilized NLRP3, ASC, and caspase 1/11 knockout (KO) mice to demonstrate the functional significance of inflammasome activity during CNS S. aureus infection. ASC and caspase 1/11 KO animals were exquisitely sensitive, with approximately 50% of mice succumbing to infection within 24 h. Unexpectedly, the survival of NLRP3 KO mice was similar to wild-type animals, suggesting the involvement of an alternative upstream sensor, which was later identified as absent in melanoma 2 (AIM2) based on the similar disease patterns between AIM2 and ASC KO mice. Besides IL-1ß, other key inflammatory mediators, including IL-6, CXCL1, CXCL10, and CCL2 were significantly reduced in the CNS of AIM2 and ASC KO mice, implicating autocrine/paracrine actions of IL-1ß, as these mediators do not require inflammasome processing for secretion. These studies demonstrate a novel role for the AIM2 inflammasome as a critical molecular platform for regulating IL-1ß release and survival during acute CNS S. aureus infection.


Subject(s)
Brain Abscess/immunology , Inflammasomes/physiology , Methicillin-Resistant Staphylococcus aureus/immunology , Nuclear Proteins/physiology , Staphylococcal Infections/immunology , Animals , Apoptosis Regulatory Proteins , Brain Abscess/metabolism , Brain Abscess/microbiology , CARD Signaling Adaptor Proteins , Carrier Proteins/genetics , Carrier Proteins/physiology , Caspase 1/deficiency , Caspase 1/physiology , Caspases/deficiency , Caspases/physiology , Caspases, Initiator , Cytokines/metabolism , Cytoskeletal Proteins/deficiency , Cytoskeletal Proteins/physiology , DNA, Bacterial/immunology , DNA-Binding Proteins , Disease Susceptibility , Female , Immunity, Innate , Inflammation Mediators/physiology , Interleukin-1beta/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Microglia/metabolism , Models, Immunological , NLR Family, Pyrin Domain-Containing 3 Protein , Nuclear Proteins/deficiency , Phenotype , Staphylococcal Infections/metabolism
20.
Mediators Inflamm ; 2013: 480739, 2013.
Article in English | MEDLINE | ID: mdl-23997430

ABSTRACT

Cytokines and chemokines are proteins that coordinate the immune response throughout the body. The dysregulation of cytokines and chemokines is a central feature in the development of neuroinflammation, neurodegeneration, and demyelination both in the central and peripheral nervous systems and in conditions of neuropathic pain. Pathological states within the nervous system can lead to activation of microglia. The latter may mediate neuronal and glial cell injury and death through production of proinflammatory factors such as cytokines and chemokines. These then help to mobilize the adaptive immune response. Although inflammation may induce beneficial effects such as pathogen clearance and phagocytosis of apoptotic cells, uncontrolled inflammation can result in detrimental outcomes via the production of neurotoxic factors that exacerbate neurodegenerative pathology. In states of prolonged inflammation, continual activation and recruitment of effector cells can establish a feedback loop that perpetuates inflammation and ultimately results in neuronal injury. A critical balance between repair and proinflammatory factors determines the outcome of a neurodegenerative process. This review will focus on how cytokines and chemokines affect neuroinflammation and disease pathogenesis in bacterial meningitis and brain abscesses, Lyme neuroborreliosis, human immunodeficiency virus encephalitis, and neuropathic pain.


Subject(s)
Chemokines/metabolism , Cytokines/metabolism , Inflammation/metabolism , Neuralgia/immunology , Neurodegenerative Diseases/immunology , Animals , Astrocytes/cytology , Brain Abscess/immunology , Encephalitis/immunology , HIV Infections/immunology , Humans , Lyme Neuroborreliosis/immunology , Meningitis, Bacterial/immunology , Meningitis, Pneumococcal/microbiology , Microglia/immunology , Phagocytosis , Signal Transduction , Staphylococcus aureus/metabolism
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