Eubacterium rectale Attenuates HSV-1 Induced Systemic Inflammation in Mice by Inhibiting CD83.

The purpose of this study was to determine whether administration of the microorganism Eubacterium rectale (E. rectale) could regulate dendritic cell (DC) activation and systemic inflammation in herpes simplex virus type 1-induced Behçet's disease (BD). E. rectale, butyrate-producing bacteria, was administered to BD mice. Peripheral blood leukocytes (PBL) and lymph node cells were isolated and analyzed by flow cytometry. 16S rRNA metagenomic analysis was performed in the feces of mice to determine the differences in the composition of the microbial population between normal and BD mice. Serum cytokine levels were measured by enzyme-linked immunosorbent assay. The frequency of DC activation marker CD83 positive cells was significantly increased in PBL of BD mice. Frequencies of CD83+ cells were also significantly increased in patients with active BD. 16S rRNA metagenomic analysis revealed different gut microbiota composition between normal and BD mice. The administration of E. rectale to BD mice reduced the frequency of CD83+ cells and significantly increased the frequency of NK1.1+ cells with the improvement of symptoms. The co-administration of colchicine and E. rectale also significantly reduced the frequency of CD83+ cells. Differences in gut microbiota were observed between normal mice and BD mice, and the administration of E. rectale downregulated the frequency of CD83, which was associated with BD deterioration. These data indicate that E. rectale could be a new therapeutic adjuvant for BD management.

Trends of HIV/Syphilis/HSV-2 seropositive rate and factors associated with HSV-2 infection in men who have sex with men in Shenzhen, China: A retrospective study.

OBJECTIVES: To analyze the trends of HIV/syphilis/HSV-2 seropositive rate and explore the related factors with HSV-2 infection to provide the basis for adjusting STD intervention strategies and formulating prevention and control measures among MSM in Shenzhen. METHODS: Time-location sampling was conducted among MSM in Shenzhen in 2012, 2014, 2016, and 2018. Data on demographics, sexual behaviors and the laboratory test results of HIV, syphilis, HSV-2 were collected. The χ2 trend test was used to analyze the trends of HIV/syphilis/HSV-2 seropositive rate. The binary logistic regression model was used to explore the factors associated with HSV-2 infection. RESULTS: The seropositive rate of HIV fell significantly from 15.9% in 2012 to 8.7% in 2018 (Ptrend = 0.003), syphilis seropositive rate was significantly decreased from 20.4% in 2012 to 14.8% in 2018 (Ptrend = 0.025), HSV-2 seropositive rate had no significant change (16.7% in 2012 to 14.0% in 2018; Ptrend = 0.617). In principal component logistic regression analysis showed that FAC1_1 (X1 = Ever had sex with female, X2 = Gender of first sexual partner, X3 = Marital status, X4 = Age group), FAC2_1 (X5 = Education, X6 = Monthly income (RMB), X7 = Frequency of condom use in anal sex with men in the past 6 months), and FAC4_1 (X9 = History of STDs) were significantly associated with HSV-2 infection. CONCLUSIONS: The seropositive rates of HIV and syphilis have dropped significantly but are still high. HSV-2 seropositive rate had no significant change and maintained a high level. It is necessary to continue strengthening HIV and syphilis interventions among MSM in Shenzhen. HSV-2 detection and intervention are urgently required for MSM, which might be another effective biological strategy further to control the HIV epidemic among MSM in Shenzhen.

Herpes simplex virus infection, Acyclovir and IVIG treatment all independently cause gut dysbiosis.

Herpes simplex virus 1 (HSV) is a ubiquitous human virus resident in a majority of the global population as a latent infection. Acyclovir (ACV), is the standard of care drug used to treat primary and recurrent infections, supplemented in some patients with intravenous immunoglobulin (IVIG) treatment to suppress infection and deleterious inflammatory responses. As many diverse medications have recently been shown to change composition of the gut microbiome, we used Illumina 16S rRNA gene sequencing to determine the effects of ACV and IVIG on the gut bacterial community. We found that HSV, ACV and IVIG can all independently disrupt the gut bacterial community in a sex biased manner when given to uninfected C57BL/6 mice. Treatment of HSV infected mice with ACV or IVIG alone or together revealed complex interactions between these drugs and infection that caused pronounced sex biased dysbiosis. ACV reduced Bacteroidetes levels in male but not female mice, while levels of the Anti-inflammatory Clostridia (AIC) were reduced in female but not male mice, which is significant as these taxa are associated with protection against the development of graft versus host disease (GVHD) in hematopoietic stem cell transplant (HSCT) patients. Gut barrier dysfunction is associated with GVHD in HSCT patients and ACV also decreased Akkermansia muciniphila, which is important for maintaining gut barrier functionality. Cumulatively, our data suggest that long-term prophylactic ACV treatment of HSCT patients may contribute to GVHD and also potentially impact immune reconstitution. These data have important implications for other clinical settings, including HSV eye disease and genital infections, where ACV is given long-term.

Cervicitis: etiología, diagnóstico y tratamiento / Cervicitis: Etiology, diagnosis and treatment

La cervicitis es un cuadro de inflamación del cuello uterino. Suele ser causada por un agente infeccioso, generalmente de transmisión sexual. Frecuentemente es asintomática, y la infección silente puede originar complicaciones del tracto genital superior. Los síntomas suelen ser inespecíficos, y los más significativos son aumento del flujo vaginal y/o sangrado intermenstrual. Para su diagnóstico existen sistemas comerciales basados en técnicas moleculares que incluyen la casi totalidad de los patógenos conocidos asociados a cervicitis, aunque los cultivos no deben abandonarse por la necesidad de realizar estudios de sensibilidad a los antibióticos. Se recomienda iniciar un tratamiento empírico que incluya C.trachomatis y N. gonorrhoeae en el caso de mujeres con elevado riesgo de infección por dichos patógenos, sobre todo si el seguimiento no está asegurado o no se dispone de pruebas diagnósticas adecuadas. En mujeres con bajo riesgo el tratamiento deberá ajustarse a los resultados de las pruebas microbiológicas

Cervicitis is the inflammation of the cervix. It is usually caused by an infectious agent, usually sexually transmitted. Cervicitis is frequently asymptomatic and silent infection can cause complications of the upper genital tract. The symptoms are usually nonspecific, the most significant being an increase in vaginal discharge and/or intermenstrual bleeding. For its diagnosis, there are commercial systems based on molecular techniques that include almost all of the known pathogens associated with cervicitis, although cultures should not be abandoned due to the need to conduct studies of susceptibility to antibiotics. It is recommended to initiate an empirical antibiotic therapy that covers C.trachomatis and N. gonorrhoeae in the case of women at high risk of infection by these pathogens, especially if the follow-up is not assured or adequate diagnostic tests are not available. In women with low risk of sexually transmitted infection, antibiotic therapy should be adjusted to the results of the microbiological results

Simultaneous candida albicans and herpes simplex virus type 2 esophagitis in a renal transplant recipient.

Renal transplant recipients are prone to opportunistic infections due to iatrogenic immunosuppression. Infectious esophagitis can present as an opportunistic infection in the post-transplant period. Common pathogens are candida, herpes simplex virus (HSV) and cytomegalovirus (CMV). Having a dual infection is uncommon and the diagnoses can be missed at initial presentation. Our patient, a 29-year-old African-American woman, status post deceased-donor-kidney transplant presented with difficulty and pain in swallowing with clinical features suggestive of candida esophagitis, confirmed by fungal culture. She did not get better with antifungal treatment. On further testing, the patient was found to have HSV-2 infection of the oesophagus as well. She received both fluconazole as well as acyclovir that lead to complete resolution of her symptoms. In the right clinical setting, esophagitis can be caused by more than one organism present at the same time and a high level of suspicion is warranted.

Added value of ultra-deep sequencing (UDS) approach for detection of genotypic antiviral resistance of herpes simplex virus (HSV).

Classically, Sanger sequencing is considered the gold standard for detection of HSV drug resistance mutations (DRMs). As a complementary method, ultra-deep sequencing (UDS) has an improved ability to detect minor variants and mixed populations. The aim of this work was to apply UDS performed on MiSeq® Illumina platform to the detection of HSV DRMs and to the evaluation of the subpopulation diversity in clinical samples in comparison with Sanger sequencing. A total of 59 HSV-positive clinical samples (31 HSV-1 and 28 HSV-2) recovered from 50 patients mainly immunocompromised (70%) were retrospectively analyzed. Remarkably, UDS analysis revealed significant differences of relative abundance according to the type of DRMs within TK and Pol: natural polymorphisms and amino acid changes associated with resistance to antivirals were identified as high-abundant mutations (>96%), whereas TK frameshifts conferring resistance to ACV were systematically detected at lower abundance (≈80%). This work also revealed that UDS can detect low-frequency DRMs and provides extensive information on viral population composition.

UL23, UL30, and UL5 characterization of HSV1 clinical strains isolated from hematology department patients.

Genotypic diagnosis of HSV drug resistance can be performed routinely in a clinically relevant time. Nevertheless, data about HSV mutations (polymorphism or resistance) is not exhaustive which hinders the interpretation of such tests. The UL23, UL30, and UL5 genes are of greatest interest as these encode, respectively, thymidine kinase, DNA polymerase, and helicase, which, if mutated may affect the effectiveness of acyclovir, foscarnet, cidofovir, and helicase-primase inhibitors. The present study aimed to extensively characterize UL23, UL30, and UL5 genes. A total of 239 clinical HSV1 recovered from patients admitted to the hematology departments of the Lyon teaching hospitals were included in this single-center retrospective study. Drug resistance was evaluated using the neutral red dye-uptake assay, and sequencing using the Sanger method. Additional information on HSV1 natural polymorphism and resistance is now available. Twenty-two amino acid substitutions related to polymorphism were described on UL23 (E43A, L50M, L68R, Q109K, A133V, A136N, S150L, D258N, S263L, P280S, N301S, A316S, M322L, I326V, D330A, D338H, Q342H, T344I, Q349R, V352L, R370W, E371D), and 6 amino acid substitutions on UL30 (G641R, G645D, E649G, G679D, R681L, I966M). Moreover, the UL23 substitution L242P was added to ACV resistance-related mutations. There were 12 substitutions on UL23 (A37S, V70M, S74L, H151N, P154S, P155Q, L159R, E225L, Y248H, Q270R, N303Y, M372I), and 8 on UL5 (L49I, L138V, S173L, A280T, A575V, V600A, A602T, D862N) that remain of unclear significance with regards to drug resistance. The mean (±standard deviation, SD) number of natural polymorphisms in UL23 was 2.53 (±2.55), in UL30 it was 0.83 (±1.02), and in UL5 it was 5.00 (±1.59) There was no association between HSV1 phenotype and the frequency of substitutions. The results reported herein provide valuable new information concerning HSV1 mutations that will assist the interpretation of genotypic assays.

Rapid detection of herpes simplex virus-1 from bronchoalveolar lavage fluids using loop-mediated isothermal amplification (LAMP) / Detección rápida del virus herpes simple-1 en lavado broncoalveolar mediante loop-mediated isothermal amplification (LAMP)

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Infections of the esophagus: an update on risk factors, diagnosis, and management.

Infectious esophagitis is a leading cause of esophagitis worldwide. While esophageal infections have traditionally been associated with immunocompromised patients, these disorders are becoming increasingly recognized in immunocompetent individuals. The three most common etiologies of infectious esophagitis are Candida, herpes simplex virus, and cytomegalovirus. Human papilloma virus infection can also involve the esophagus in the form of ulcerative lesions and papillomas. Less common etiologies include various other fungal, bacterial, and viral organisms. This review provides a comprehensive update on risk factors, diagnosis, and management of both common and less common infections of the esophagus.

Unique causes of esophageal inflammation: a histopathologic perspective.

Gastroenterologists frequently perform endoscopic esophageal mucosal biopsies for pathologic diagnosis in patients experiencing symptoms of esophagitis. The more common causes of esophagitis diagnosed on esophageal mucosal biopsy include reflux esophagitis, eosinophilic esophagitis, and infectious esophagitis caused by Candida albicans, herpes simplex virus, and/or cytomegalovirus. However, there are several causes of esophagitis seen less frequently by pathologists that are very important to recognize. We discuss unique types of esophageal inflammation, including acute bacterial esophagitis, esophageal manifestations of dermatologic diseases, medication-induced esophageal injury, and sloughing esophagitis; and we review their clinical and histopathologic features.

Saccharomyces boulardii CNCM I-745 supplementation reduces gastrointestinal dysfunction in an animal model of IBS.

BACKGROUND: We evaluated the effect of Saccharomyces boulardii CNCM I-745 on intestinal neuromuscular anomalies in an IBS-type mouse model of gastrointestinal motor dysfunctions elicited by Herpes Simplex Virus type 1 (HSV-1) exposure. METHODS: Mice were inoculated intranasally with HSV-1 (102 PFU) or vehicle at time 0 and 4 weeks later by the intragastric (IG) route (108 PFU). Six weeks after IG inoculum, mice were randomly allocated to receive oral gavage with either S. boulardii (107 CFU/day) or vehicle. After 4 weeks the following were determined: a) intestinal motility using fluorescein-isothiocyanate dextran distribution in the gut, fecal pellet expulsion, stool water content, and distal colonic transit of glass beads; b) integrity of the enteric nervous system (ENS) by immunohistochemistry on ileal whole-mount preparations and western blot of protein lysates from ileal longitudinal muscle and myenteric plexus; c) isometric muscle tension with electric field and pharmacological (carbachol) stimulation of ileal segments; and d) intestinal inflammation by levels of tumor necrosis factor α, interleukin(IL)-1ß, IL-10 and IL-4. RESULTS: S. boulardii CNCM I-745 improved HSV-1 induced intestinal dysmotility and alteration of intestinal transit observed ten weeks after IG inoculum of the virus. Also, the probiotic yeast ameliorated the structural alterations of the ENS induced by HSV-1 (i.e., reduced peripherin immunoreactivity and expression, increased glial S100ß protein immunoreactivity and neuronal nitric oxide synthase level, reduced substance P-positive fibers). Moreover, S. boulardii CNCM I-745 diminished the production of HSV-1 associated pro-inflammatory cytokines in the myenteric plexus and increased levels of anti-inflammatory interleukins. CONCLUSIONS: S. boulardii CNCM I-745 ameliorated gastrointestinal neuromuscular anomalies in a mouse model of gut dysfunctions typically observed with irritable bowel syndrome.

Clinical courses of herpes simplex virus-induced urethritis in men.

We retrieved clinical data of 13 men having herpes simplex virus (HSV)-induced non-gonococcal urethritis (NGU) without visible herpetic lesions. They visited a clinic in Sendai, Japan, between April 2013 and December 2015. All the men complained of dysuria. Meatitis was observed in 9 of the 13 men. Mononuclear cells were observed in the urethral smears from 9 men. The 13 men were treated with azithromycin or sitafloxacin regimen. First-voided urine (FVU) specimens became negative for HSV in 8 of the 10 men who returned to the clinic after antibacterial treatment, and urethritis symptoms were alleviated. However, herpetic lesions were observed at the follow-up visits in 3 men, and 2 of them were still positive for HSV in their FVU. HSV could be a cause of acute urethritis without causing visible herpetic lesions. The shedding of HSV from the urethra would spontaneously cease with alleviation of urethritis symptoms in most cases of HSV-induced NGU without antiviral therapy. However, new herpetic lesions could be developed in some cases. Early antiviral therapy is beneficial for patients with HSV infections. The development of meatitis and the mononuclear cell response in the urethral smear could be helpful to diagnose HSV-induced NGU. Therefore, we should presumptively initiate anti-HSV therapy for patients with signs and symptoms suggestive of HSV-induced NGU at their first presentation.

[THE SPECTRUM OF MARKERS OF HERPES VIRAL INFECTIONS AND ALGORITHM OF THEIR LABORATORY DIAGNOSTIC IN CHILDREN WITH INFLAMMATORY PROCESSES OF UPPER RESPIRATORY WAYS AND ENT-ORGANS].

The purpose of study is to explore markers of persistent herpes viral infections in children with inflammatory processes of upper respiratory ways and ENT-organs. The sampling included 118 examined patients aged from 1 month to 17 years. The complex of standardized viral, immunological, molecular genetic methods was applied to detect (to exclude) herpes infection: cytomegalovirus infection, Epstein-Barre virus infection, simplex herpes virus infection. The diagnostic algorithm of examination of children with diseases of upper respiratory ways for herpes infection is presented. The dominating significance of simplex herpes virus and Epstein-Barre virus and also Staphylococcus aureus and Streptococcus haemolyticus-ß group A at the analysis of microbial landscape. In 83.9% of children with diseases of upper respiratory ways chronic infections of simplex herpes virus, Epstein-Barre virus, cytomegalovirus; in39.39% - mixed-infection; in 41.03% - combination of simplex herpes virus and Epstein-Barre virus infections; in 33.33% - combination of simplex herpes virus and cytomegalovirus infections; in 7.69% - combination of simplex herpes virus and Epstein-Barre virus and cytomegalovirus infections; in 17.94% - combination of Epstein-Barre virus and cytomegalovirus infections; The particularity of course of persistent herpes infection in children had to do with absence of specific symptoms of nosologic form in 59.2% of cases. The results of analysis of smears from nasopharynx of children infected with herpes viruses permitted to detect: Staphylococcus aureus in 36.36%; Streptococcus haemolyticus-ß in 32.32%; Streptococcus haemolyticus-α in 11.11%; Candida albicans of mucous membranes in 4.04% of children. The viral bacterial mixed-infection was detected in 44.44%. The laboratory signs of activity of immune inflammation were detected: increasing of content of TNАα and decreasing of level of IFNγ. The results of study substantiate necessity of individual approach to therapy of children with diseases of upper respiratory ways and ENT-organs and with implementation of complex of curative rehabilitating activities.The purpose of study is to explore markers of persistent herpes viral infections in children with inflammatory processes of upper respiratory ways and ENT-organs. The sampling included 118 examined patients aged from 1 month to 17 years. The complex of standardized viral, immunological, molecular genetic methods was applied to detect (to exclude) herpes infection: cytomegalovirus infection, Epstein-Barre virus infection, simplex herpes virus infection. The diagnostic algorithm of examination of children with diseases of upper respiratory ways for herpes infection is presented. The dominating significance of simplex herpes virus and Epstein-Barre virus and also Staphylococcus aureus and Streptococcus haemolyticus-ß group A at the analysis of microbial landscape. In 83.9% of children with diseases of upper respiratory ways chronic infections of simplex herpes virus, Epstein-Barre virus, cytomegalovirus; in39.39% - mixed-infection; in 41.03% - combination of simplex herpes virus and Epstein-Barre virus infections; in 33.33% - combination of simplex herpes virus and cytomegalovirus infections; in 7.69% - combination of simplex herpes virus and Epstein-Barre virus and cytomegalovirus infections; in 17.94% - combination of Epstein-Barre virus and cytomegalovirus infections; The particularity of course of persistent herpes infection in children had to do with absence of specific symptoms of nosologic form in 59.2% of cases. The results of analysis of smears from nasopharynx of children infected with herpes viruses permitted to detect: Staphylococcus aureus in 36.36%; Streptococcus haemolyticus-ß in 32.32%; Streptococcus haemolyticus-α in 11.11%; Candida albicans of mucous membranes in 4.04% of children. The viral bacterial mixed-infection was detected in 44.44%. The laboratory signs of activity of immune inflammation were detected: increasing of content of TNАα and decreasing of level of IFNγ. The results of study substantiate necessity of individual approach to therapy of children with diseases of upper respiratory ways and ENT-organs and with implementation of complex of curative rehabilitating activities.

Influence of Staphylococcus aureus attachment to the herpes simplex virus infected cells.

The purpose of this study was to investigate the response of HeLa cells to the interaction with inactivated Staphylococcus aureus cells and live challenge with herpes simplex virus (HSV).The results of this study are indicating that the interaction between the HeLa cells and S. aureus inactivated whole cells could modulate the host cell apoptosis and cytokine production, and therefore, influence the progression of HSV infection. The pre-treatment of HeLa cells with heat inactivated bacterial whole cells protects them from the occurrence of HSV mediated cytopathic effect, while the post viral infection treatment with bacterial cells prevents the high activation of bax/bcl-2 apoptotic pathway, a process that could change the fate of the infectious process triggered by the virus, and eventually reduce its multiplication rate. The pre-treatment of HeLa monolayer with inactivated bacterial cells 24 hours before the viral infection is increasing the expression level of TNF-a, IL-6 and IL-8 pro-inflammatory cytokines genes, also suggesting that bacterial antigens could contribute to the decrease of viral multiplication rate.

Proanthocyanidin-enriched extract from Myrothamnus flabellifolia Welw. exerts antiviral activity against herpes simplex virus type 1 by inhibition of viral adsorption and penetration.

AIM OF THE STUDY: Extracts from the aerial parts of the South African resurrection plant Myrothamnus flabellifolia Welw. have been used traditionally against infections of the upper respiratory tract and skin diseases. A polyphenol-enriched extract was investigated for potential antiviral effects against herpes simplex virus type 1 (HSV-1) and adenovirus, and the underlying mode of action was to be studied. MATERIALS AND METHODS: Antiviral effects of an acetone-water extract (MF) from Myrothamnus flabellifolia on HSV-1 and adenovirus type 3 were tested in infected Vero cells by plaque reduction assay, MTT test and immunofluorescence. The influence of the extract on the HSV-1 envelope glycoprotein D was shown by Western blot. Organotypic full thickness skin models consisting of multilayer skin equivalents were used for the investigation of MF effects on HSV-1 replication. RESULTS: MF exhibited strong antiviral activity against HSV-1. The HSV-1-specific inhibitory concentration (IC(50)) was determined as 0.4 µg/mL and the cytotoxic concentration (CC(50)) against Vero cells as 50 µg/mL. A selectivity index (SI) (ratio of CC(50) to IC(50)) of approximately 120 was calculated when MF was added to the virus inoculum for 1h at 37°C prior to infection. The replication of adenovirus 3 was not affected by MF. MF abolished virus entry into the host cell by blocking viral attachment to the cell surface. When added after attachment at a concentration of >6 µg/mL, the extract also inhibited penetration of HSV-1 into the host cell. Polyphenolic compounds from MF directly interacted with viral particles, leading to the oligomerisation of envelope proteins as demonstrated for the essential viral glycoprotein D (gD). Using organotypic full thickness tissue cultures, it was shown that treatment of HSV-1 infected cultures with the MF resulted in reduced viral spread. CONCLUSIONS: A polyphenol-enriched extract from Myrothamnus flabellifolia strongly acts against HSV-1 by blocking viral entry into the cells.

A systematic review of viral infections associated with oral involvement in cancer patients: a spotlight on Herpesviridea.

PURPOSE: Our aim was to evaluate the literature for the prevalence of and interventions for oral viral infections and, based on scientific evidence, point to effective treatment protocols. Quality of life (QOL) and economic impact were assessed if available in the articles reviewed. METHODS: Our search of the English literature focused on oral viral infections in cancer patients within the timeframe of 1989-2007. Review methods were standardized. Cohort studies were used to determine the weighted prevalence of oral viral infection in cancer patients. The quality of selected articles were assessed and scored with respect to sources of bias, representativeness, scale validity, and sample size. Interventional studies were utilized to determine management guidelines. Literature search included measures of QOL and economic variables. RESULTS: Prevalence of oral herpes simplex virus (HSV) infection in neutropenic patients was higher than in patients treated with radiotherapy for head and neck cancer (49.8% vs. 0%, respectively). In patients treated with radiochemotherapy for head and neck cancer, the prevalence of oral HSV infection increases up to 43.2% (CI, 0-100%). Prevalence of HSV infection was higher when oral ulcers existed. Information about other oral viral infections is sparse. There was a significant benefit of using acyclovir to prevent HSV oral infection (at 800 mg/day). Various dosing protocols of valacyclovir achieved prevention of HSV reactivation (500 or 1,000 mg/day). The prevalence of HSV reactivation was similar for acyclovir and valacyclovir. No information about impact on QOL and economic burden was available. CONCLUSIONS: Acyclovir and valacyclovir are equally effective in preventing oral HSV infection. Neutropenic patients, who were primarily treated for hematological malignancies in the studies reviewed, are at a greater risk for viral infection.

Role of infection in the pathogenesis of Alzheimer's disease: implications for treatment.

While our understanding of the neuropathology of Alzheimer's disease continues to grow, its pathogenesis remains a subject of intense debate. Genetic mutations contribute to a minority of early-onset autosomal dominant cases, but most cases are of either late-onset familial or sporadic form. CNS infections, most notably herpes simplex virus type 1, Chlamydophila pneumoniae and several types of spirochetes, have been previously suggested as possible aetiological agents in the development of sporadic Alzheimer's disease but with little consistent evidence. However, peripheral infections may have a role to play in accelerating neurodegeneration in Alzheimer's disease by activating already primed microglial cells within the CNS. Potential pharmacological interventions could aim at modification of this peripheral inflammatory response through targeting various agents involved in this inflammatory pathway. However, benefit could also be gained clinically through the meticulous detection, treatment and prevention of infections in individuals either alone or in combination with anti-inflammatory therapy.

Herpes simplex virus type 1 dysregulates anti-fungal defenses preventing monocyte activation and downregulating toll-like receptor-2.

We investigated the interplay occurring between pathogens in the course of dual infections, using an in vitro model in which the THP-1 monocytic cell line is first infected with HSV-1 and then exposed to Ca or Cn. These three pathogens share some pathogenic features: they cause opportunistic infections, target macrophages and are neurotropic. Here, we show that HSV-1-infected THP-1 cells exhibited augmented phagocytosis against the two opportunistic fungi but reduced capability to counteract fungal infection: the better ingestion by monocytes was followed by facilitated fungal survival and replication. Reduced IL-12 production was also observed. Cytofluorimetric analysis showed that HSV-1-infected monocytes exhibit: (i) downregulated TLR-2 and TLR-4, critical structures in fungal recognition; (ii) reduced expression of CD38 and CD69, known to be important markers of monocyte activation; and (iii) enhanced expression of apoptosis and necrosis markers, in the absence of altered cell proliferation. Overall, these findings imply that HSV-1 infection prevents monocyte activation, thus leading to a significant dysfunction of the monocyte-mediated anti-Candida response; HSV-1 induced apoptosis and necrosis of monocytes further contribute to this impairment.