Differing and temporally specific roles of different MMPs after CNS injury, along with the implication of MMPs in neuropathic pain states following spinal cord injury means the premise of broad spectrum MMP alteration warrants natural caution. Although it may be noted that the synthetic tetracycline derivative minocycline has weak broad-spectrum MMP inhibitory activity and, alongside safety, reports a nonsignificant trend towards improved neurological

and functional recovery following a phase II clinical trial as a therapeutic for spinal check details cord injury (http://www.clinicaltrials.gov/SHOW/NCT00559494), [229]. In addition, MMP substrates are extremely wide-ranging and many are highly

nonspecific. https://www.selleckchem.com/HSP-90.html As an example, while MMP-3 degrades candidate CSPGs upregulated after CNS injury, it also degrades collagen types II, III, IV, IX and X, fibronectin, laminin and elastin and activates other MMPs including MMP-1, MMP-7 and the pro-inflammatory MMP-9. In addition there is redundancy; aggrecan, as an example, is cleaved by MMP-1, -2, -3, -7, -8, -9, -11, -13, -14, -15, -19, -20 [230]. Due to broad specificity and wide-ranging orchestrated and inter-regulatory roles of MMPs, attention is also drawn to other, more specific, endogenous matrix remodelling enzymes. MMPs belong to the metzincin superfamily of metalloproteinases, also including astacins, ADAMs (a protein with a disintegrin and metalloprotease domain) and ADAM-TS (an ADAM with a thrombospondin-like motif) proteases. Of

particular interest, ADAMTS-4 reverses the proteoglycan-mediated inhibition of neurite outgrowth in vitro [231] and in vivo, ADAMTS-4 has been shown to promote functional recovery after moderate thoracic contusion in the rat when delivered intrathecally via osmotic mini-pump [232]; interestingly, functional improvement was Beta adrenergic receptor kinase of the same magnitude to that seen with the more commonly used enzyme chondroitinase (the use of chondroitinase as a tool to promote repair following CNS injury will be discussed below). With increasing specificity in terms of proteolytic target, a recent study reports use of the mammalian enzyme arylsulphatase B (ARSB) (N-acetylgalactosamine 4-sulphatase) which removes the C-4-S moieties from CSPGs, previously reported to be inhibitory to neuronal growth [185]. Following moderate and severe thoracic spinal compression injuries in the mouse, a single intraspinal injection of human ARSB removed immunoreactivity for C-4-S which was associated with increased serotonergic and tyrosine hydroylase positive axon sprouting and functional locomotor recovery [233]. The authors suggest that ARSB has interesting advantages in that its enzymatic activity is optimal at acidic pH and the CNS injury environment has been reported to display mild acidosis [234].

After co-culture with CII for 72 h, CD4+ T cells were isolated from SMNCs derived from

CII immunized mice and transcript levels of four Notch receptors, including Notch1, Notch2, Notch3 and Notch4, were assessed. We found that CII restimulation see more up-regulated Notch3 transcription significantly in CD4+ T cells. To further confirm the specific role of Notch3, we added specific neutralizing antibody to Notch3 to the SMNCs restimulation system and found that anti-Notch3 treatment reduced T cell proliferation and the frequency of Th1 and Th17 cells. These results indicate that Notch3 plays an important role in CII-specific T cell proliferation and expansion. Over-expression of the Notch3 intracellular domain in T cells has been reported to induce differentiation of IFN-γ-secreting Th1 but reduced IL-4-secreting Th2 cells. When Notch3 expression was inhibited with anti-sense-DNA, the Th1-type differentiation was also inhibited [17]. Our results were partly different from another research group, which explored the role of Notch signalling in myelin-reactive CD4+ T cells using the EAE model, and found that both Notch1 and Notch3 were up-regulated upon specific antigen restimulation, although Notch1 inhibition did not affect the proliferation and differentiation DMXAA of autoreactive

T cells [13]. These different data may result from the use of different antigens as well as different animal models. Nevertheless, we agree with the important role of Notch3 in antigen-specific Th1 and Th17 cell expansion other than Treg cells. Notch signalling is initiated by ligand–receptor interaction

between neighbouring cells. We next asked which Notch ligands are involved in CII-specific T cell proliferation and differentiation by the addition of Delta-like 1-Fc and Jagged1-Fc fusion proteins into SMNCs co-cultured with CII from CII immunized mice. Our results indicate that it should be Delta-like 1 rather than Jagged1 that promotes the collagen-specific Th1- and Th17-type expansion. In EAE, pathogenic Th1 and Th17 cells develop in the central nervous system, causing autoimmunity. Resminostat Specific antibodies against Delta-like 1, which attenuated EAE, have opposite effects to antibodies against Jagged1 which exacerbated EAE [18]. Maekawa et al. reported that Delta-like 1 interaction with Notch3 on CD4+ T cells promoted development towards the Th1 phenotype [17]. However, Delta-like 4-expressing dendritic cells (DCs), when activated with Toll-like receptor (TLR) ligands or Mycobacterium antigens, can promote the generation of Th17 cells through activation of the Th17 cell-specific transcription factor retinoic acid-related orphan receptor γ-T (RORγt) [19,20]. The specific interactions of Notch ligands and receptors on T cells may be regulated by the expression pattern of Notch ligands on neighbour cells [17].

At the functional level, rat splenocytes and IHLs have been shown to secrete IFN-γ and IL-4 in response to stimulation with α-GalCer [12, 13] in a CD1d-dependent fashion ([13] and this study). α-GalCer-loaded mouse or human CD1d tetramers bind very poorly to the rat iNKT-TCR [12] (Monzon-Casanova, Herrmann, unpublished data). This is in contrast to the mouse and the human, both of which show CD1d/iNKT-TCR cross-species reactivity

[1], but it explains why a discrete population was not observed among rat IHLs using mouse CD1d tetramers [12]. Furthermore, former attempts to identify rat iNKT cells using surrogate markers have also failed as no cell population has yet been found with the features predicted for iNKT cells based on their mouse counterparts. Instead, rat NKR-P1A/B-positive SP600125 price T cells are found in the spleen and the liver at similar frequencies, show no BV8S2 or BV8S4 bias, produce IFN-γ but not IL-4, and most of them express CD8β [9, 12, 14-16]. In the present study, newly generated rat CD1d dimers allowed us to identify rat iNKT cells for the first time in the F344 inbred rat strain.

Importantly, these cells are more similar to human than mouse iNKT cells in terms of frequencies, CD8 expression, and expansion upon in vitro stimulation with α-GalCer. In addition, we found a nearly complete lack of iNKT cells in the widely used LEW rat strain. These findings identify the rat as a closely matching animal model to study the biology and the therapeutic use of iNKT cells in humans.

The negligible binding of rat iNKT-TCR to Fludarabine price α-GalCer-loaded mouse CD1d tetramers [14] prompted us to generate syngeneic CD1d dimers. Rat and mouse CD1d dimers were loaded with α-GalCer or vehicle only (DMSO) as a control and were used to stain IHLs derived from F344 rats and from C57BL/6 mice (Fig. 1). Rat α-GalCer-CD1d dimers Staurosporine price bound to a small but distinct population of F344 IHLs, which was missing when rat vehicle-CD1d dimers were used. As expected, very few rat cells were stained by mouse α-GalCer-CD1d dimers (when comparing with the vehicle control), but in contrast, a subpopulation of mouse iNKT cells was stained with rat α-GalCer-CD1d dimers. These results are consistent with our previous functional data [12]. The differences between the iNKT-cell frequencies of C57BL/6 mice and F344 rats are noteworthy. In C57BL/6 mice, more than 50% of all αβ T cells in the liver (30% of total IHLs) were detected with mouse α-GalCer-CD1d dimers, while in F344 rats, iNKT cells constituted only 1.05% of all αβ T cells (0.24% of total IHLs; Fig. 1 and Supporting Information Table 1). In both species positive α-GalCer-CD1d-dimer-stained T cells expressed low TCR levels, a feature of iNKT cells. In line with the particular homing preferences of iNKT cells, more iNKT cells were found in the liver (0.24%) as compared with what was found in the spleen (0.013%) of F344 inbred rats (Fig.

We included HD patients without diagnosed dementia who were 50 years or older. Using established methods, we classified participants’ in CI categories (none to mild and moderate to selleck chemical severe) based on results of a neurocognitive battery. We collected demographic and laboratory data from dialysis unit records, as well as all BP measurements from 12 dialysis sessions. We tested the association between CI and BP fluctuation, adjusting for demographic and laboratory variables. Our study enrolled 39 patients; 25 had moderate to severe CI.

The normal to mild CI group and the moderate to severe patients had similar degrees of BP fluctuation (average minimum systolic BP (SBP): 107.6 ± 18.7 vs 110.2 ± 18.6 mmHg, maximum drop in SBP: 32.6 ± 10.2 vs 35.4 ± 15.0 mmHg; proportion of sessions with SBP < 90 mmHg: 0.2 ± 0.3 vs 0.2 ± 0.3; average change in SBP, pre to post HD: 10.2 ± 12.4 vs 11.8 ± 16.4 mmHg, all P > 0.55). There was no association between BP variables and

performance on individual selleck chemicals llc cognitive tests. Multivariable analysis showed that older age and non-Caucasian race were associated with a reduction in cognitive scores. There was no cross-sectional association between dialytic BP changes and cognitive performance. “
“A 51-year-old woman received an ABO blood type-incompatible renal transplant. She was administered rituximab and basiliximab and underwent plasma exchanges for induction therapy, followed by administration of tacrolimus, mycophenolate mofetil and methylprednisolone as maintenance immunosupression therapy. A planned renal biopsy 2 years after transplantation revealed infiltration of plasma cells in the renal interstitium,

although there was no next ‘storiform’ fibrosis surrounding these cells. There were also no findings of rejection, BK virus nephropathy, or atypical plasma cells. Immunohistochemical stainings showed a large number of IgG4-positive plasma cells, most of which expressed kappa-type light chains. A CT scan showed a mass at the renal hilum. The serum IgG4 level was high. Based on these findings, the patient was suspected of having IgG4-related kidney disease. Nine months after the biopsy, her serum creatinine level increase to 1.56 mg/dL and the dose of methylprednisolone was therefore increased to 16 mg/day. Three months after this increase in steroid, a CT scan showed the hilum mass had disappeared. A follow-up biopsy 5 months later showed that infiltration of plasma cells in the renal interstitium had decreased markedly, although focal and segmental severely fibrotic lesions with IgG4-positive plasma cells were observed. Serum IgG4 levels decreased immediately after the increase in steroid dose and remained <100 mg/dL despite a reduction in methylprednisolone to 6 mg/day. Serum creatinine levels also remained stable at around 1.6 mg/dL.

This study found no increase in the complication rate and flap ischemia time using the rib-sparing IMV exposure technique. ©

2014 Wiley Periodicals, Inc. Microsurgery 34:448–453, 2014. “
“A 4-year-old girl who sustained the hemiplegic cerebral palsy and subsequent spasticity in the left upper extremity underwent the C7 nerve root rhizotomy and the contralateral C7 nerve root transfer to the ipsilateral middle trunk of brachial plexus through an interpositional sural nerve graft. In a 2-year follow-up, the results showed a reduction in spasticity and an improvement in extension power of the elbow, the wrist, and the second to fifth fingers. Scores from both Quality of Upper Extremity Skills Test and Modified Ashworth Scale tests had been significantly improved during follow-up. The outcomes from this case provided the evidence that combined the C7 nerve root rhizotomy and contralateral healthy C7 nerve root transfer Bortezomib to the ipsilateral middle trunk of brachial plexus not only partially released flexional spasticity but also strengthened extension power of the spastic upper extremity in children with the cerebral palsy. © 2011 Wiley-Liss, Silmitasertib Inc. Microsurgery, 2011. “
“To date, nerve stumps have been dissected at the proximal side of the donor muscle for reinnervation of the muscle in free neurovascular

muscle transfer. Herein, we examined the use of the distal thoracodorsal nerve, dissected from the muscle belly at the distal side of the latissimus dorsi muscle, for the reinnervation of muscle. The rat right latissimus dorsi muscle was employed as the model for our study. Twenty Wistar rats were used in this Dolichyl-phosphate-mannose-protein mannosyltransferase study. A rectangular muscle segment was dissected with the distal stump of dominant thoracodorsal nerve. After rotation of muscle, the distal nerve stump was sutured to a severed proximal recipient thoracodorsal nerve (n = 5). The degree of reinnervation through the distal nerve stump was compared with control groups that received proximal-to-proximal nerve sutures (n = 5), nerves that were not severed (n = 5), and severed nerves that were not sutured (n = 5) using electrophysiological,

histological, and muscular volume assessments. Reinnervation of the distal nerve stump was confirmed by the contraction of the muscle following electrical stimulation and electromyography. Crossing of axons into motor endplates was confirmed by histology. Results of these assays were similar to that of the proximal nerve suture group. The volume of muscle in the distal nerve suture group was not significant different from that of the proximal nerve suture group (P = 0.63). It was demonstrated that the distal stump of the thoracodorsal nerve can be used to innervate segmented latissimus dorsi muscle. This novel procedure for the reinnervation of transplanted muscle deserves further investigations. © 2013 Wiley Periodicals, Inc.

Background: MK is a novel cytokine, which is pathologically

implicated in a number of inflammatory disease processes including kidney disease. It has potential as both a biomarker and a biological therapeutic target in acute and CKD. To date there is little data on MK levels in humans with CKD. Method: This is a prospective, observational study. Plasma, serum and urine samples were simultaneously obtained from CKD outpatients and healthy Small molecule library supplier volunteers (HV), stored at −70°C, and assayed for MK levels using a commercially available MK-ELISA kit (Cellmid Ltd, Sydney, Australia). MK levels were compared between 2 severity groups, divided as HV and stage 1–2, compared with a second group of stage 3–5. Result: Samples were obtained from 20 HV and 126 CKD patients. Serum MK levels were significantly higher in the CKD stage 3–5 group than the HV or CKD 1–2 group (3009 (SD = 1942) vs 870 pg/mL (SD = 384) P < 0.001). Urine MK levels were significantly higher in the CKD stage 3–5 group than the HV or CKD 1–2 group (6008 (SD = 13462) vs 654 pg/mL (SD = 1517) P ≤ 0.001). Conclusion: Serum and urine Midkine levels are elevated in stage 3–5 CKD patients compared to non-CKD or lesser stages 1–2. Whether this is association, or reflecting

part of the pathological process Cell Cycle inhibitor requires further exploration. 161 MIDKINE LEVELS CAN BE MEASURED IN EITHER PLASMA OR SERUM V CAMPBELL1,2,3, NA GRAY1,3, C ANSTEY2,3, R GATELY1, C CLARK1,2, E NOBLE1, K MAHADEVAN1,2, PR HOLLETT1,2, A POLLOCK1, D JONES4, S HALL5 1Renal Unit, Nambour General Hospital, Nambour, Queensland; 2Sunshine Coast Clinical School, The University of Queensland, Nambour, Queensland; 3Intensive Care Unit, Nambour General hospital, Nambour, Queensland, Australia; 4Cellmid Ltd; 5Pathology North – Hunter New England Aim: To compare Midkine oxyclozanide (MK) levels when measured in plasma and serum. Background: Midkine is a novel cytokine, which is pathologically implicated in a number of inflammatory and malignant disease processes. Levels have usually been measured in serum, however protein assays can be performed on either plasma or serum. Because of the increasing number of both

serum and plasma banks being stored as part of large clinical trials, validating the assay in both sample types would allow further investigation of this cytokine. Methods: Plasma and serum samples were simultaneously obtained from chronic kidney disease (CKD) outpatients and healthy volunteers (HV), stored at −70°C, and assayed for MK levels using a commercially available MK-ELISA kit (Cellmid Ltd, Sydney, Australia). Data were analysed using multivariate linear regression. Results: Samples were obtained from 20 HV and 126 CKD patients. The causes of CKD included 26% diabetes, 37% hypertension/vascular, 9% glomerulonephritis, 5% polycystic disease, and 24% other. The CKD stages ranged from 1–5, with the majority being stage 3–4.

Other confounders in the analysis included type of initial CNI (cyclosporine or tacrolimus) and antimetabolite agent (mycophenolate

mofetil or azathioprine or none), as well AZD5363 as transplanting centres and transplant period. Transplant period was divided into four cohorts for analysis (i.e. 1995–1997, 1998–2000, 2001–2003, 2004–2005). Transplanting centres were categorized into the five transplanting states in Australia including Western Australia, New South Wales, Victoria, Queensland and South Australia. The report of comorbid medical conditions was collected at the commencement of renal replacement therapy. The clinical outcomes of this study were acute rejection occurring in the first 6 months post-transplant, overall graft survival (including death-censored graft failure (DCGF) and death with functioning graft (DFG)), patient survival and estimated GFR (eGFR) calculated by Modification of Diet in Renal Disease formula14 at 1 and 5 years post-transplant. Data on acute rejection were collected only from see more 1997. For the purpose of this study, outcome data of all patients were censored at December

2006. Results were expressed as frequency (percentage) for categorical data or as mean and standard deviation for continuous data. Comparisons of baseline characteristics between the use of IL-2Ra were made by chi-square test or Fisher’s exact test, as

appropriate. Acute Sitaxentan rejection was modelled using log-binomial regression to estimate relative risk (RR). Linear regression was used to examine eGFR at 1 and 5 years by estimating differences in mean. Graft and patient survival were examined using standard survival methodology using Kaplan–Meier methods, including Cox regression for adjusted analyses. Log–rank tests were used to test equality of survival curves. As DFG and DCGF are competing risks, differences in the cumulative incidences of DFG and DCGF were tested using the Pepe and Mori test. All point estimates are presented with 95% confidence interval (95% CI). The covariates included in the adjusted models include donors’ characteristics (age, source and gender), recipients’ characteristics (gender, BMI, age, diabetes mellitus, vascular disease, smoking, time on dialysis), transplant centres and period. Statistical analysis was performed using Stata/IC 10 statistical software program (Stata Corporation, College Station, TX, USA). Two-tailed P-values of less than 0.05 were considered statistically significant. Of the low-risk recipients, 218 of 1220 (18%) received IL-2Ra induction therapy whereas 883 of 3204 (28%) intermediate-risk recipients received IL-2Ra.

2+ cells. Control mice only received T-cell-depleted BM cells. Mice were monitored for appearance, body weight and survival on a weekly or daily basis. To examine proliferation of donor-derived T cells in recipients, BM cells and 5 × 105 CD3+ T cells from KO or WT mice were co-injected intravenously into γ-irradiated recipient mice. Five days after injection, cells were prepared

from spleens and livers of recipient mice (the latter cells were prepared as described previously[19]) and pulsed with H-2Kb-associated OVA peptide (1 μg/ml) for 30 min. After washing, donor-derived T cells were labelled fluorescently with phycoerythrin-conjugated anti-H-2Kb-SIINFEKL antibody and FITC-conjugated Fer-1 mw antibody directed against CD4, CD8 or CD69; positive cells were counted by flow cytometry. To examine SD-4 expression on conventional T (Tconv) cells and regulatory T (Treg) cells, CD4+ T cells were purified from spleen cells of WT C57BL/6 mice using a CD4+ T-cell isolation kit (Miltenyi) and split into two batches: one left untreated and the other cultured for 2 days in 96-well plates (2 × 105 cells/well) pre-coated with anti-CD3 and anti-CD28 antibody (each 1 μg/ml). Cells were surface stained to detect SD-4 (or PD-1) -positive cells and then treated with learn more cell fixation/permeabilization solution (eBioscience),

followed by staining with allophycocyanin-conjugated anti-Foxp3 antibody. To examine the influence of SD-4 deletion on T-cell-suppressive activity of Treg cells, CD4+ CD25neg Tconv cells and CD4+ CD25+ Treg cells were isolated by fractionating purified CD4+ T cells (from spleen cells of WT or KO mice) using anti-CD25 antibody and anti-biotin microbeads (Miltenyi Biotec): Treg cells were collected from eluate of the magnetic column, and Tconv cells from the

pass through (purity was > 95%). Tconv cells from WT mice (5 × 105 cells/well) were labelled with CFSE and stimulated with anti-CD3 antibody (5 μg/ml) in the presence of an equal number of γ-irradiated WT spleen cells (as APC). To this culture, varying numbers of Treg cells isolated from WT or KO mice were added. Suppression of Tconv-cellproliferation by Treg cells was determined by flow cytometric analysis of CFSE dilution after 72 hr. Data are presented as means ± SD. The significance of differences between experimental STK38 variables was determined using a two-tailed Student’s t-test. All data shown are representative of at least two independent experiments. The absence of published information regarding the impact of SD-4 gene disruption on leucocyte development led us to compare the relative proportions of leucocyte sub-populations (CD4+ and CD8+ T cells, CD19+ B cells and CD11c+ DC) in BM, spleen and lymph nodes of mice aged 6 weeks (Fig. 1a–c). There were no significant differences between WT and KO mice. We also measured ratios of double-positive versus single-positive T cells in thymus and those of CD4+ versus CD8+ T cells in spleen and lymph nodes (Fig. 1d).

The authors declare that they

have no competing interests. “
“Bacterial biofilms have been implicated in multiple clinical scenarios involving infection of implanted foreign bodies, but have been little studied after hernia repair. We now report a case of revision inguinal herniorrhaphy complicated by chronic pain at the operated site without any external indication of infection. Computed tomographic imaging revealed a contrast-enhancing process in the left groin. Subsequent surgical exploration found an inflammatory focus centered on implanted porcine xenograft material and nonabsorbable monofilament sutures placed at the previous surgery. Confocal microscopic examination of these materials with Live/Dead staining demonstrated abundant viable bacteria in biofilm configuration. The removal of these INCB024360 order materials and direct closure of the recurrent hernia defect eliminated Selleckchem Acalabrutinib the infection and resolved the patient’s complaints. These results demonstrate that implanted monofilament suture and xenograft material can provide the substratum for a chronic biofilm infection. Bacterial biofilms are communities of microorganisms that can attach to both abiotic and biological (e.g. mucosal) surfaces in humans (Hall-Stoodley et al., 2004). Biofilms have

been noted to be contributing or causative factors in a wide variety of infectious processes, especially those associated with implanted foreign bodies, including orthopedic prostheses (Stoodley et al., 2005, 2008), neurosurgical drains and shunts (Stoodley et al., 2010), vascular and peritoneal catheters (Gorman et al., 1994), etc. Biofilm bacteria differ from their planktonic counterparts in significant ways: they have a much higher (by orders of magnitude) resistance to conventional antibiotics, they

are able to evade host humoral and cellular immunological mechanisms [largely through their encapsulating matrix of extracellular polymeric substance (EPS)], and they can frequently prove difficult to detect using standard clinical microbiological culture techniques (Hall-Stoodley et al., 2004). These properties render the diagnosis and treatment Carnitine palmitoyltransferase II of infections with a biofilm etiology problematic (Hall-Stoodley & Stoodley, 2009). Although biofilms have been observed on numerous types of prosthetic surfaces, there has thus far been comparatively little examination of the materials used in hernia repairs. Herniorrhaphy, the surgical repair of hernias, is usually accomplished using suture material to close the hernia defect directly, or through the use of some type of an interpositional surgical mesh. More recently, surgeons have begun to use so-called ‘biological meshes,’ that is, acellular matrices derived from human or animal donor tissues, as materials with which to reconstruct abdominal wall hernia defects (Hiles et al., 2009).

Naïve CD4+ T (TN) cells are maintained in the periphery via the common γ-chain family

cytokine IL-7 and weak antigenic signals. However, it is not clear how memory CD4+ T-cell subsets are maintained in the periphery and which factors are responsible for the maintenance. To examine the homeostatic mechanisms, CFSE-labeled CD4+CD44highCD62Llow effector memory T (TEM) cells were transferred this website into sublethally-irradiated syngeneic C57BL/6 mice, and the systemic cell proliferative responses, which can be divided distinctively into fast and slow proliferations, were assessed by CFSE dye dilution. We found that the fast homeostatic proliferation of TEM cells was strictly regulated by both antigen and OX40 costimulatory signals and that the slow proliferation was dependent on IL-7. The simultaneous blockade of both OX40 and IL-7 signaling completely inhibited the both fast and slow proliferation. The antigen- and OX40-dependent fast proliferation preferentially expanded IL-17-producing helper T cells (Th17 cells). Thus, OX40 and IL-7 play synergistic, but distinct roles in the homeostatic proliferation of CD4+ TEM cells. “
“Type I interferons (IFN-I) have been known for decades for their indispensable role in curtailing viral infections. It is, however, now also increasingly recognized that IFN-I is detrimental to the host in combating a number of bacterial infections. We have previously

reported that viral infections induce partial lymphocyte activation, characterized by significant increases in the cell Sorafenib mouse surface expression of CD69 and CD86, but not CD25. This systemic partial activation of lymphocytes, mediated by IFN-I, is rapid and is followed by a period of IFN-I unresponsiveness. Here we propose that

IFN-I exhaustion that occurs soon after a primary viral infection may be a host response SSR128129E protecting it from secondary bacterial infections. Since it was first shown in 1957 that IFN-I ‘interferes’ with viral replication within host cells [1], it has become one of the best studied cytokine. The beneficial effects of IFN-I are well appreciated in numerous viral experimental models as inducers of antiviral state. Type I interferon is one of the few successful antiviral treatments in therapeutic clinical use, as in chronic hepatitis C infections [2]. Viral infections of most somatic cells result in an early synthesis of IFN-I production. Specialized cells called plasmacytoid dendritic cells (pDCs) are the major IFN-I producers [3] and mediate systemic IFN-I responses following viral infections [4]. The primary role of IFN-I is to limit initial viral replication and to facilitate subsequent adaptive immune responses. IFN-I is a multifunctional cytokine that positively influences cells of both innate and adaptive immunity and therefore is considered as a bridge that links innate and adaptive immunity (reviewed in [5]). With a few exceptions of chronic viral infections [6, 7], most studies agree that IFN-I is protective against acute viral infections.