Decreased quality of care for Staphylococcus aureus bacteremia during the COVID-19 pandemic.

OBJECTIVES: Staphylococcus aureus bacteremia (SAB) is one of the most frequent bloodstream infections. High mortality of SAB can be significantly reduced by regular infectious disease (ID) consultations and appropriate clinical management. Because the pandemic of coronavirus disease 2019 (COVID-19) has had a negative impact on hospital ID service, it can be assumed that it has also led to decreased quality of care for SAB patients. METHODS: This study enrolled all (n = 68) patients with proven SAB who were hospitalized in Military University Hospital, Prague, in 2019 and 2020 and the quality of care indicators for SAB patients were compared. RESULTS: A total of 33 and 35 patients with SAB were hospitalized in our hospital in 2019 and 2020, respectively. The significant difference between the pandemic year 2020 and year 2019 was in ID consultations performed (74% vs. 100%; p = 0.002) and fulfilment of all quality of care indicators (66% vs. 93%; p = 0.012). Next, higher in-hospital mortality was observed in 2020 than in 2019 (6% vs. 23%; p = 0.085). There was no significant difference in the percentages of patients with performed echocardiographic examinations (66% vs. 83%; p = 0.156) and collected follow-up blood cultures (85% vs. 94%; p = 0.428). In addition, there was no difference between the two years in the adequate antibiotic therapy, sources, and bacterial origin of SAB. CONCLUSIONS: The quality of care of SAB patients significantly decreased during the COVID-19 pandemic in our institution.

Acute phase of COVID-19 is associated with elevated plasmablasts in the blood.

OBJECTIVES: The study was aimed at the characterization of humoral immunity in acute SARS-CoV-2 infection. BACKGROUND: Humoral immunity plays a central role in the protection from infection due to SARS-CoV-2, causative agent of coronavirus diseases 2019 (COVID-19). PATIENTS AND METHODS: In 24 adult patients hospitalized with COVID-19, the functional subsets of circulating B-lymphocytes and SARS-CoV-2 specific IgA and IgG antibodies were analyzed using a flow cytometry and immunoassays, respectively. RESULTS: Circulating plasmablasts and memory B-lymphocytes were significantly elevated and regulatory B-lymphocytes significantly decreased in the patients in comparison with 11 age- and sex-matched SARS-CoV-2 seronegative healthy adults. Next, circulating plasmablasts correlated negatively with the levels of SARS-CoV-2 specific IgG antibodies, which were detectable in 9 out of 15 tested patients. In addition, SARS-CoV-2 specific IgA antibodies were detectable in 13 of 15 tested patients and did not demonstrate correlation with any B-lymphocyte subset. CONCLUSION: Severe course of COVID-19 is associated with significant changes of phenotypes of circulating B-lymphocytes and elevated circulating plasmablasts correlate with decreased SARS-CoV-2-specific IgG antibodies (Tab. 2, Fig. 3, Ref. 14).

Salmonella Paratyphi Infection: Use of Nanopore Sequencing as a Vivid Alternative for the Identification of Invading Bacteria.

In our study we present an overview of the use of Oxford Nanopore Technologies (ONT) sequencing technology on the background of Enteric fever. Unlike traditional methods (e.g., qPCR, serological tests), the nanopore sequencing technology enables virtually real-time data generation and highly accurate pathogen identification and characterization. Blood cultures were obtained from a 48-year-old female patient suffering from a high fever, headache and diarrhea. Nevertheless, both the initial serological tests and stool culture appeared to be negative. Therefore, the bacterial isolate from blood culture was used for nanopore sequencing (ONT). This technique in combination with subsequent bioinformatic analyses allowed for prompt identification of the disease-causative agent as Salmonella enterica subsp. enterica serovar Paratyphi A. The National Reference Laboratory for Salmonella (NIPH) independently reported this isolate also as serovar Paratyphi A on the basis of results of biochemical and agglutination tests. Therefore, our results are in concordance with certified standards. Furthermore, the data enabled us to assess some basic questions concerning the comparative genomics, i.e., to describe whether the isolated strain differs from the formerly published ones or not. Quite surprisingly, these results indicate that we have detected a novel and so far, unknown variety of this bacteria.

Chronic Hepatitis C Virus Infection Modulates the Transcriptional Profiles of CD4+ T Cells.

BACKGROUND: Chronic hepatitis C (CHC) is associated with altered cell-mediated immune response. OBJECTIVE: The aim of the study was to characterize functional alterations in CD4+ T cell subsets and myeloid-derived suppressor cells (MDSCs) during chronic hepatitis C virus (HCV) infection. Methodology. The expression levels of the lineage-defining transcriptional factors (TFs) T-bet, Gata3, Rorγt, and Foxp3 in circulating CD4+ T cells and percentages of MDSCs in peripheral blood were evaluated in 33 patients with CHC, 31 persons, who had spontaneously cleared the HCV infection, and 30 healthy subjects. Analysis. The CD4+ T cells TFs T-bet (T-box expressed in T cells), Foxp3 (Forkhead box P3 transcription factor), Gata3 (Gata-binding protein 3), and Rorγt (retinoic-acid-related orphan receptor gamma) and activation of CD8+ T cells, as well as percentages of MDSCs, were measured by multicolor flow cytometry after intracellular and surface staining of peripheral blood mononuclear cells with fluorescent monoclonal antibodies. RESULT: The patients with CHC had significantly lower percentages of CD4+ T cells expressing Rorγt and Gata3 and higher percentages of Foxp3-expressing CD4+ T cells than healthy controls and persons who spontaneously cleared HCV infection. The ratios of T-bet+/Gata3+ and Foxp3+/Rorγt+ CD4+ T cells were the highest in the patients with CHC. In the patients with CHC, the percentages of Gata3+ and Rorγt+ CD4+ T cells and the percentages of T-bet+ CD4+ T cells and CD38+/HLA-DR+ CD8+ T cells demonstrated significant positive correlations. In addition, the percentage of CD38+/HLA-DR+ CD8+ T cells correlated negatively with the percentage of MDSCs. CONCLUSION: Chronic HCV infection is associated with downregulation of TFs Gata3 and Rorγt polarizing CD4+ T cells into Th2 and Th17 phenotypes together with upregulation of Foxp3 responsible for induction of regulatory T cells suppressing immune response.

Frequent Recurrences of Genital Herpes Are Associated with Enhanced Systemic HSV-Specific T Cell Response.

OBJECTIVES: Genital herpes simplex virus (HSV) infection is controlled by HSV-specific T cells in the genital tract, and the role of systemic T cell responses is not fully understood. Thus, we analysed T cell responses in patients with recurrent genital herpes (GH). METHODS: T cell responses to HSV-1 and HSV-2 native antigens and the expression of HLA-DR and CD38 molecules on circulating CD8+ T cells were analysed in adults with high frequency of GH recurrences (19 patients) and low frequency of GH recurrences (7 patients) and 12 HSV-2 seronegative healthy controls. The study utilized the interferon-γ Elispot assay for measurement of spot-forming cells (SFC) after ex vivo stimulation with HSV antigens and flow cytometry for analysis of the expression of activation markers in unstimulated T cells. RESULTS: The patients with high frequency of GH recurrences (mean number of recurrences of 13.3 per year) had significantly enhanced HSV-specific T cell responses than the HSV-2 seronegative healthy controls. Moreover, a trend of higher numbers of SFC was observed in these patients when compared with those with low frequency of GH recurrences (mean number of recurrences of 3.3 per year). Additionally, no differences in CD38 and HLA-DR expression on circulating CD8+ T cells were found among the study groups. CONCLUSIONS: Frequency of GH recurrences positively correlates with high numbers of systemic HSV-specific T cells.

Selected Biomarkers Correlate with the Origin and Severity of Sepsis.

The microbial etiology and source of sepsis influence the inflammatory response. Therefore, the plasma levels of cytokines (IL-6, IL-8, and IL-10), chemokines (CCL2/MCP-1, MIP-1ß), heparin-binding protein (HBP), soluble CD14 (sCD14), and cortisol were analyzed in blood from septic patients obtained during the first 96 hours of intensive care unit hospitalization. The etiology was established in 56 out of a total of 62 patients enrolled in the study. Plasma concentrations of MCP-1, sCD14, IL-6, and IL-10 were significantly higher in patients with community-acquired pneumonia (CAP; n = 10) and infective endocarditis (IE; n = 11) compared to those with bacterial meningitis (BM; n = 18). Next, cortisol levels were higher in IE patients than in those with BM and CAP, and at one time point, cortisol was also higher in patients with gram-negative sepsis when compared to those with gram-positive infections. Furthermore, cortisol and MCP-1 levels correlated positively with the daily measured SOFA score. In addition, HBP levels were significantly higher in patients with IE than in those with BM. Our findings suggest that MCP-1, sCD14, IL-6, IL-10, cortisol, and HBP are modulated by the source of sepsis and that elevated MCP-1 and cortisol plasma levels are associated with sepsis-induced organ dysfunction.

[New definitions for sepsis and septic shock - Sepsis-3].

The article discusses new definitions for sepsis and septic shock called Sepsis-3. The definitions are put in the historical and factual context of the 1992 definition and their extended 2003 version. Also mentioned are potential impacts on clinical practice, with it-being clear that the new definition shifts the sepsis issues more to intensive care as it emphasizes organ failure. In prehospital care, emergency departments and general wards of hospitals where patients are triaged, a new scoring system, the so-called quick SOFA, may be used. In this approach, stress is placed on impaired consciousness, a drop in systolic pressure and tachypnea but its role in more precise identification is yet to be verified in common clinical practice.

Cytokines and chemokines as biomarkers of community-acquired bacterial infection.

Routinely used biomarkers of bacterial etiology of infection, such as C-reactive protein and procalcitonin, have limited usefulness for evaluation of infections since their expression is enhanced by a number of different conditions. Therefore, several inflammatory cytokines and chemokines were analyzed with sera from patients hospitalized for moderate bacterial and viral infectious diseases. In total, 57 subjects were enrolled: 21 patients with community-acquired bacterial infections, 26 patients with viral infections, and 10 healthy subjects (control cohorts). The laboratory analyses were performed using Luminex technology, and the following molecules were examined: IL-1Ra, IL-2, IL-4, IL-6, IL-8, TNF- α , INF- γ , MIP-1 ß , and MCP-1. Bacterial etiology of infection was associated with significantly (P < 0.001) elevated serum concentrations of IL-1Ra, IL-2, IL-6, and TNF- α in comparison to levels observed in the sera of patients with viral infections. In the patients with bacterial infections, IL-1Ra and IL-8 demonstrated positive correlation with C-reactive protein, whereas, IL-1Ra, TNF- α , and MCP-1 correlated with procalcitonin. Furthermore, elevated levels of IL-1Ra, IL-6, and TNF- α decreased within 3 days of antibiotic therapy to levels observed in control subjects. The results show IL-1Ra as a potential useful biomarker of community-acquired bacterial infection.

Elevated regulatory T cells after antibiotic treatment of infectious spondylodiscitis as biomarker of recovery?

Dysregulated systemic immune responses during infectious spondylodiscitis (IS) may impair microbial clearance and bone resorption. Therefore, the aim of the study was to examine whether circulating regulatory T cells (Tregs) are elevated during IS and whether their frequency is associated with alterations in T cells and the presence of markers of bone resorption in the blood. A total of 19 patients hospitalized with IS were enrolled in this prospective study. Blood specimens were obtained during hospitalization and 6 weeks and 3 months after discharge. Flow cytometric analysis of CD4 and CD8 T cell subsets, the percentage of Tregs and serum levels of collagen type I fragments (S-CrossLap) were performed. Out of 19 enrolled patients with IS, microbial etiology was confirmed in 15 (78.9%) patients. All patients were treated with antibiotics for a median of 42 days, and no therapy failure was observed. Next, a significant serum C-reactive protein (S-CRP) decrease during the follow-up was observed, whereas the frequencies of Tregs remained higher than those of controls at all-time points (p < 0.001). In addition, Tregs demonstrated a weak negative correlation with S-CRP and S-CrossLap levels were within the norm at all-time points. Circulating Tregs were elevated in patients with IS and this elevation persisted even after the completion of antibiotic therapy. Moreover, this elevation was not associated with treatment failure, altered T cells, or increased markers of bone resorption.

Specific immune responses after BNT162b2 mRNA vaccination and COVID-19 infection.

Although vaccines against COVID-19 are effective tools in preventing severe disease, recent studies have shown enhanced protection after vaccine boosters. The aim of our study was to examine the dynamics and duration of both humoral and cellular immune responses following a three-dose regimen of the BNT162b2 mRNA vaccine. In a longitudinal prospective study we enrolled 86 adults who received the BNT162b2 vaccine, 35 unvaccinated individuals with a history of mild COVID-19 and a control group of 30 healthy SARS-CoV-2 seronegative persons. We assessed the SARS-CoV-2-specific T cell responses and IgG production up to 12 months post the third BNT162b2 dose in 24 subjects. The vaccinated group had significantly higher IgG antibody levels after two doses compared to the convalescent group (p<0.001). After the third dose, IgG levels surged beyond those detected after the second dose (p<0.001). Notably, these elevated IgG levels were maintained 12 months post the third dose. After two doses, specific T cell responses were detected in 87.5% of the vaccinated group. Additionally, there was a significant decrease before the third dose. However, post the third dose, specific T cell responses surged and remained stable up to the 12-month period. Our findings indicate that the BNT162b2 vaccine induces potent and enduring humoral and cellular responses, which are notably enhanced by the third dose and remain persistant without a significant decline a year after the booster. Further research is essential to understand the potential need for subsequent boosters.

Heparin-binding protein as a biomarker of circulatory failure during severe infections: a report of three cases.

We report 3 cases of disease - leptospirosis, tropical malaria and fulminant meningococcaemia - associated with high serum concentrations of heparin-binding protein (HBP) and haemodynamic instability. Furthermore, HBP kinetics were observed for the first 3 days in survivors and were correlated with improvement in clinical condition.

Preservation of immune function and anti-hepatitis C virus (HCV) immune responses after liver transplantation in HIV-HCV coinfected patients (ANRS-HC08 "THEVIC" trial).

BACKGROUND/AIMS: Liver transplantation (LT) in immune-suppressed human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfected patients is feasible but raises questions regarding the severity of HCV recurrence on the liver graft and preservation of immune function. We investigated whether LT is deleterious to the immune system. METHODS: Fourteen HIV-HCV coinfected patients (HIV viral load [VL] <50 copies/ml; median CD4 count of 276/mm(3) pretransplantation) were grafted for HCV-cirrhosis and followed over 2 years. Nine patients received anti-HCV therapy post-transplantation. HCV and HIV VLs and degree of acute and chronic hepatitis were monitored. Peripheral blood T-cell phenotypes and interferon-gamma (IFN-gamma) immune responses against opportunistic pathogens, HCV, and HIV-1 p24 were evaluated. RESULTS: Median HCV VLs, CD4 counts, T-cell subsets, and IFN-gamma-producing T-cell frequencies against opportunistic pathogens and HIV-1 p24 did not change over time. HCV-specific T cells were observed ex vivo in two patients pretransplantation and in two others post-transplantation. HCV-specific in vitro amplification enabled the detection of HCV-specific IFN-gamma-producing responses in three further patients post-transplantation. Anti-HCV responses were observed independently of anti-HCV therapy and were undetectable in patients with severe hepatitis or liver fibrosis. CONCLUSIONS: These results demonstrate that LT in HIV-HCV coinfected patients is not deleterious to the immune system and does not alter immune responses directed against HCV, HIV, or opportunistic pathogens.

[Selected aspects of the immunopathogenesis of HIV infection]. / Vybrané aspekty imunopatogeneze HIV infekce.

This review describes a current view on immunopathogenesis of HIV infection including potential causes of immune failure in control of the infection. Above all, the role of different components of immune system is being discussed. Their interplay is disturbed during interaction with the virus and determines the course of the infection. HIV primary infection causes depletion of CD4+ effector memory T cells in extra-lymphoid compartments that are first replaced by CD4+ T cells proliferation. However, at the end the regenerative capacity is exhausted and opportunistic infections occur. A crucial role in controlling HIV replication is played by HIV-specific cytotoxic CD8+ T cells that eliminate virus-infected cells and delay progression of the infection. Thus, the majority of vaccination strategies is based on stimulation of a potent cytotoxic response. Chronic nonspecific immune activation that gradually destroys functional organization of immune system has been well documented in HIV+ patients. Also, several circulating microbial products from gastrointestinal tract have been recently suggested as a cause of chronic immune activation following depletion of mucosal CD4+ T cells and intestinal mucosa damage. Better understanding of immunopathogenetic mechanisms of HIV infection is necessary to determine further aims for immunotherapeutic interventions and vaccination strategies.

Calprotectin and calgranulin C serum levels in bacterial sepsis.

The aim of this study was to evaluate the serum levels of calprotectin and calgranulin C and routine biomarkers in patients with bacterial sepsis (BS). The initial serum concentrations of calprotectin and calgranulin C were significantly higher in patients with BS (n = 66) than in those with viral infections (n = 24) and the healthy controls (n = 26); the level of calprotectin was found to be the best predictor of BS, followed by the neutrophil-lymphocyte count ratio (NLCR) and the level of procalcitonin (PCT). The white blood cell (WBC) count and the NLCR rapidly returned to normal levels, whereas PCT levels normalized later and the increased levels of calprotectin, calgranulin C, and C-reactive protein persisted until the end of follow-up. Our results suggest that the serum levels of calprotectin are a reliable biomarker of BS and that the WBC count and the NLCR are rapid predictors of the efficacy of antimicrobial therapy.

Cortisol levels in cerebrospinal fluid correlate with severity and bacterial origin of meningitis.

INTRODUCTION: Outcomes following bacterial meningitis are significantly improved by adjunctive treatment with corticosteroids. However, little is known about the levels and significance of intrathecal endogenous cortisol. The aim of this study was to assess cortisol as a biological and diagnostic marker in patients with bacterial meningitis. METHODS: Forty-seven consecutive patients with bacterial meningitis and no prior treatment were evaluated. For comparison, a group of 37 patients with aseptic meningitis and a group of 13 healthy control individuals were included. RESULTS: The mean age of the bacterial meningitis patients was 42 years, and the mean Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation II, and Sequential Organ Failure Assessment scores on admission were 12, 13 and 4, respectively. Altogether, 40 patients (85%) were admitted to the intensive care unit, with a median (interquartile range) length of stay of 8 (4 to 15) days. A bacterial etiology was confirmed in 35 patients (74%). The median (interquartile range) cortisol concentration in cerebrospinal fluid (CSF) was 133 (59 to 278) nmol/l. CSF cortisol concentrations were positively correlated with serum cortisol levels (r = 0.587, P < 0.001). Furthermore, CSF cortisol levels correlated with Acute Physiology and Chronic Health Evaluation II score (r = 0.763, P < 0.001), Sequential Organ Failure Assessment score (r = 0.650, P < 0.001), Glasgow Coma Scale score (r = -0.547, P < 0.001) and CSF lactate levels (r = 0.734, P < 0.001). CSF cortisol was only weakly associated with intrathecal levels of IL-6 (r = 0.331, P = 0.02) and IL-8 (r = 0.296, P < 0.05). CSF cortisol levels in bacterial and aseptic meningitis significantly differed (P < 0.001). The CSF cortisol concentration of 46.1 nmol/l was found to be the optimal cutoff value for diagnosis of bacterial meningitis. CONCLUSION: CSF cortisol levels in patients with bacterial meningitis are highly elevated and correlate with disease severity. Moreover, our findings also suggest that intrathecal cortisol may serve as a valuable marker in discriminating between bacterial and aseptic meningitis.

Effect of antiviral treatment of chronic hepatitis C on the frequency of regulatory T cells, T-cell activation, and serum levels of TGF-beta.

The aim was to analyze T-regulatory cells (Tregs), activated CD8(+) T cells, and transforming growth factor-beta (TGF)-ß in hepatitis C patients. We enrolled 31 patients with chronic genotype 1 hepatitis C virus (HCV) infection, 30 seropositive persons with spontaneous HCV elimination, and 23 healthy volunteers. The patients were examined at the beginning of the interferon-alpha (IFN-α)-based therapy (baseline) and at weeks 4 (W4) and 12 (W12) of the therapy. The percentage of Tregs and the expression of activation markers CD38 and HLA-DR on CD8(+) T cells were analyzed in the peripheral blood by flow cytometry. Serum levels of TGF-ß were measured in a multiplex assay using flow cytometry. The percentage of Tregs in patients was higher than in controls and seropositive persons. Similarly, the percentage of CD8(+) T cells expressing CD38 and HLA-DR was higher in patients compared with controls and seropositive persons. Chronic HCV infection is associated with elevated circulating Tregs and activated CD8(+) T cells. During IFN-α-based therapy these cells gradually increase, whereas TGF-ß serum levels decrease.

The Effect of Latent Toxoplasma gondii Infection on the Immune Response in HIV-Infected Patients.

A relationship between latent toxoplasmosis and the immune system during HIV disease is poorly understood. Therefore, the aim of this follow-up study was to characterize immunological parameters in HIV-infected patients with latent toxoplasmosis and noninfected individuals. A total of 101 HIV-infected patients were enrolled in the study. The patients were classified into two groups based on anti-Toxoplasma gondii antibodies: a group of 55 toxoplasma-positive persons (TP) and a group of 46 toxoplasma-negative persons (TN). Absolute counts of several lymphocyte subsets decreased in the TP group, namely, T cells (p = 0.007), B cells (p = 0.002), NK cells (p = 0.009), CD4 T cells (p = 0.028), and CD8 T cells (p = 0.004). On the other hand, the percentage of CD8 T cells expressing CD38 and HLA-DR significantly increased during the follow-up in the TP group (p = 0.003, p = 0.042, resp.) as well as the intensity of CD38 and HLA-DR expression (MFI) on CD8 T cells (p = 0.001, p = 0.057, resp.). In the TN group, analysis of the kinetics of immunological parameters revealed no significant changes over time. In conclusion, the results suggest that latent T. gondii infection modulates the immune response during HIV infection.

[CD38 antigen as a marker for immunological follow-up in HIV-positive patients]. / Antigen CD38 jako ukazatel pro imunologické sledování HIV-pozitivních osob.

BACKGROUND: HIV infection causes chronic activation of cytotoxic CD8+ T-lymphocytes, which is partly responsible for the hallmark of the disease--progressive loss of CD4+ T-lymphocytes. The aim of this study was to evaluate an influence of HIV infection and long-term antiretroviral therapy (HAART) on expression of the activation molecules CD38 on CD8+ T-lymphocytes. METHODS: A group of 16 HIV-positive patients treated with HAART was followed for 12 months. Also, we examined 10 persons with a newly diagnosed HIV infection that were not treated with HAART. Expression of CD38 molecules on CD8+ T-lymphocytes was determined with five-parameter cytometric analysis using monoclonal antibodies as well as their mean fluorescence intensity (MFI). RESULTS: The percentage of CD8+/CD38+ T-lymphocytes in HIV-positive patients treated with HAART significantly decreased during the follow-up period from 46.1 I 3.7 to 35.2 I 3.8 (p = 0,01). Furthermore, the percentage of these cells correlated negatively with the number of CD4+T-lymphocytes at the beginning and the end of the study (r = -0,679, p < 0.01; r = -0,51, p = 0,05, respectively). There was no correlation between these parameters in persons with newly diagnosed HIV infection. However, the percentage of CD8+/CD38+ T-lymphocytes in these patients was significantly higher than in persons treated with HAART (68.5 I 5.3 vs. 35.2 I 3.8, p < 0,01). CONCLUSIONS: Our findings support the importance of expression of CD38 antigen on CD8+ T-lymphocytes as a biological and clinical marker of HIV infection and indicate its usefulness for monitoring of the efficacy of HAART therapy.

Different cytokine production and Toll-like receptor expression induced by heat-killed invasive and carrier strains of Neisseria meningitidis.

Neisseria meningitidis may cause severe invasive disease. The carriage state of the pathogen is common, and the reasons underlying why the infection becomes invasive are not fully understood. The aim of this study was to compare the differences between invasive and carrier strains in the activation of innate immunity. The monocyte expression of TLR2, TLR4, CD14, and HLA-DR, cytokine production, and the granulocyte oxidative burst were analyzed after in vitro stimulation by heat-killed invasive (n = 14) and carrier (n = 9) strains of N. meningitidis. The expression of the cell surface markers in monocytes, the oxidative burst, and cytokine concentrations were measured using flow cytometry. Carrier strains stimulated a higher production of inflammatory cytokines and oxidative burst in granulocytes than invasive strains (all p < 0.001), whereas invasive strains significantly up-regulated TLR2, TLR4 (p < 0.001), and CD14 (p < 0.01) expression on monocytes. Conversely, the monocyte expression of HLA-DR was higher after the stimulation by carrier strains (p < 0.05) in comparison to invasive strains. The LPS inhibitor polymyxin B abolished the differences between the strains. Our findings indicate different immunostimulatory potencies of invasive strains of N. meningitidis compared with carrier strains.