Altered serum antibody levels in children with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis.

Objectives: This study aimed to extend the literature by analyzing immunoglobulin (Ig) A, IgE, IgG, IgG2, IgG3, and IgM antibody levels in periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) patients. Patients and methods: This study retrospectively analyzed the antibody test results of 20 pediatric patients (10 males, 10 females; mean age: 2.5±1.5 years; range, 0.5 to 5.4 years) with and without flare who were initially evaluated for a number of underlying diseases due to periodic fever/infectious symptoms but then diagnosed with PFAPA between January 2015 and December 2020. Antibody levels were determined by chemiluminescence microparticle immunoassay. The results were retrospectively compared with a group of healthy children after the PFAPA diagnosis was confirmed. Results: The chemiluminescence microparticle immunoassay revealed 35%, 65%, 20%, 86.6%, and 55% of PFAPA cases with low serum levels of IgA, IgG, IgG2, IgG3, and IgM respectively, while 56.2% had high IgE levels. Moreover, low serum levels of at least two antibody classes or subclasses were reported in 80% of the PFAPA children. While cases with low IgG serum levels were with the highest incidence rates among the low IgG3 PFAPA patient population, both high IgE and low IgM cases were common in the rest of the patients. Conclusion: Our results suggest an association between PFAPA and low serum antibody levels, particularly of IgG3. Future studies are needed to confirm our conclusion.

Importance of NK Cells in Cellular and Humoral Responses Triggered by Pneumococcus Vaccination.

INTRODUCTION: Despite the success of vaccination in reducing overall rate of pneumococcal pneumonia, Streptococcus pneumoniae is still held responsible for high mortality and modality rates worldwide. Our study aimed to investigate the potential role played by NK cells in immune response generated by pneumococcal vaccination, which could contribute to the development of more effective vaccines. METHODS: The study included mice with and without NK cell depletion which were immunized with pneumococcus polysaccharide-conjugated vaccine followed by pneumococcus polysaccharide vaccine (PPV). Serum samples and splenocytes were collected from mice sacrificed 4 weeks after the last PPV dose. Serum samples were used for antibody level quantification by ELISA assay, while splenocytes were treated with PPV in vitro before monitoring CD4+ T-cell subsets (TH1, TH2, and TH17) and cytokine (IFN-γ, IL-4, and IL-17) secretion levels by flow cytometry and ELISA analysis, respectively. RESULTS: Results demonstrated reduced pneumococcal IgG and TH1 cell levels due to NK cell depletion. Nevertheless, in contrast to these observations, IFN-γ secretion levels after in vitro PPV-23 treatment of splenocytes did not exhibit any statistically significant difference between the two mice groups. CONCLUSIONS: The data indicate a positive contribution of NK cells to both T-cell and B-cell responses triggered against pneumococcal vaccination. Further studies are required to confirm our data and investigate the potential benefit of NK cell targeting in promoting vaccine efficacy, especially in the elderly population who continues to be affected significantly by pneumococcal pneumonia.

Long-COVID-19 in Asymptomatic, Non-Hospitalized, and Hospitalized Populations: A Cross-Sectional Study.

A substantial proportion of coronavirus disease 2019 (COVID-19) survivors continue to suffer from long-COVID-19 (LC) symptoms. Our study aimed to determine the risk factors for LC by using a patient population from Northern Cyprus. Subjects who were diagnosed with severe acute respiratory syndrome-2 (SARS-CoV-2) infection in our university hospital were invited and asked to fill in an online questionnaire. Data from 296 survivors who had recovered from COVID-19 infection at least 28 days prior the study was used in the statistical analysis. For determination of risk factors for "ongoing symptomatic COVID-19 (OSC)" and "Post-COVID-19 (PSC)" syndromes, the patient population was further divided into group 1 (Gr1) and group 2 (Gr2), that included survivors who were diagnosed with COVID-19 within 4-12 weeks and at least three months prior the study, respectively. The number of people with post-vaccination SARS-CoV-2 infection was 266 (89.9%). B.1.617.2 (Delta) (41.9%) was the most common SARS-CoV-2 variant responsible for the infections, followed by BA.1 (Omicron) (34.8%), B.1.1.7 (Alpha) (15.5%), and wild-type SARS-CoV-2 (7.8%). One-hundred-and-nineteen volunteers (40.2%) stated an increased frequency of COVID-19-related symptoms and experienced the symptoms in the week prior to the study. Of those, 81 (38.8%) and 38 (43.7%) were from Gr1 and Gr2 groups, respectively. Female gender, chronic illness, and symptomatic status at PCR testing were identified as risk factors for developing OSC syndrome, while only the latter showed a similar association with PSC symptoms. Our results also suggested that ongoing and persistent COVID-19-related symptoms are not influenced by the initial viral cycle threshold (Ct) values of the SARS-CoV-2, SARS-CoV-2 variant as well as vaccination status and type prior to COVID-19. Therefore, strategies other than vaccination are needed to combat the long-term effect of COVID-19, especially after symptomatic SARS-CoV-2 infection, and their possible economic burden on healthcare settings.

Immune mechanisms induced by sublingual immunotherapy in allergic respiratory diseases.

Allergic respiratory diseases (ARDs) are still a major burden on global public health. Sublingual immunotherapy (SLIT) is a mode of allergen immunotherapy (AIT) which involves administration of the allergen under the tongue, and benefits from tolerogenic properties of the oral mucosa. Studies revealed reduced levels of eosinophilia and eosinophil-dominated inflammation in airways of both animals and humans after SLIT. SLIT was also suggested to lower basophil responsiveness and innate lymphoid cell-2 function in blood samples collected from patients with ARD. Moreover, apart from shifting pathogenic type 2 (TH2) to a type 1 (TH1) and protective regulatory (Treg) polarization of helper T-cell immune response, antibody isotype switch from IgE to IgG1, IgG2, IgG4 and IgA was also reported in patients with ARD receiving SLIT. Today, the literature on SLIT-mediated activities is still scarce and more studies are required to further enlighten the mechanisms utilized by SLIT for the induction of tolerance. The aim of this review is to summarize the current knowledge about the immune-regulatory mechanisms induced by SLIT against ARDs.

The pediatric asymptomatic SARS-CoV-2 IgG seropositivity in the Turkish Republic of Northern Cyprus.

BACKGROUND: While children were initially thought to have serious contributions to the coronavirus disease 2019 (COVID-19) transmission, recent studies suggest otherwise. However, the possible effect of asymptomatic pediatric spread still has not yet received enough attention. The aim of our study was to estimate asymptomatic infection rates among children in the Turkish Republic of Northern Cyprus, by using pediatric patients admitted to a university hospital without any COVID-19-associated symptoms. METHODS: Blood samples collected from 80 pediatric patients with no symptoms and history of COVID-19 infection, who were admitted to a university hospital between September 2020 and January 2021, were included in the retrospective study. Isolated serum samples were tested by Dia.Pro SARS-CoV-2 IgG ELISA assays. RESULTS: The patient group included 40 (50%) male and 40 (50%) female patients. The average age of children was 7.6 ± 4.0 years, with min-max ages ranging from 2 to 15 years. Among the 80 patients tested, only one (1.3%) was detected positive by the Dia.Pro IgG ELISA kit. CONCLUSIONS: The asymptomatic seropositivity reported in our study suggests the use of randomly performed serologic tests to monitor SARS-CoV-2 infection among the pediatric population in schools that would contribute to the public health fight against COVID-19.

[Factors Influencing Pneumococcal Vaccination-Induced Total IgG, IgG2, and IgA Levels in Vaccinated Splenectomized Patients]. / Asili Splenektomili Hastalarda Pnömokok Asisi ile Indüklenmis Total IgG, IgG2 ve IgA Düzeylerini Etkileyen Faktörler.

Splenectomy is closely associated with a lifetime risk of pneumococcal and other encapsulated bacterial infections. In this study, it was aimed to investigate the change of antibody levels after vaccination against Streptococcus pneumoniae according to age, gender, years after splenectomy and the possible effect of splenectomy on IgG avidity. In addition the education and awareness levels of the participants about post-splenectomy vaccination and infectious diseases were also analyzed. In the first of the three phases of this study, 32 individuals with splenectomy were enrolled. The awareness of the patients about the possible risks after splenectomy was investigated with a simple questionnaire. Routine laboratory test results were obtained and clinical examinations were performed. In the second stage, total Ig values of 29 splenectomy patients were determined. In the third phase, 14 splenectomy and 5 healthy volunteers were vaccinated according to the Vaccination Practices Advisory Committee (ACIP) guidelines. Pneumococcal-specific antibody levels and IgG avidity were detected by enzyme linked immunosorbent assay (ELISA). It was determined that 68.8% of the splenectomized patients were unaware of their vaccination status and 78.2% of them were unaware of the increased risk of infectious diseases in asplenic conditions. . According to the hospital information management system, all 31 (96.87%) patients, except one, were vaccinated with PPV23. As expected, vaccinated patients exhibited high levels of vaccine-specific antibody production with IgG, IgG2, and IgA antibody concentrations of 321 ± 76.68 mg/l, 73.07 ± 8.273 mg/l, and 117.8 ± 14.94 mg/l, respectively, but unvaccinated patients had very low antibody (IgG, IgG2 and IgA antibody concentrations were 11.5 mg/l, 1.3 mg/l and 1.2 mg/l, respectively) levels. Although there was no correlation between antibody titers and gender, age groups or presence of fever history, the decrease in total IgG, IgG2 and IgA titers were strongly correlated with the time since splenectomy. Antibody titers were found to be significantly lower in splenectomized patients vaccinated more than 10 years ago. Routine laboratory results were at normal levels except for low platelet count. On the other hand, both splenectomized and healthy control subjects displayed similar IgG avidity index values (%61.8 ve %64.4% inhibition in control and splenectomized subjects, respectively) after the vaccination schedule. It was shown that post-splenectomy vaccination with PPV23 induced high levels of pneumococcus-specific antibody production that can last for more than five years. It was determined that more efforts should be made to increase the level of knowledge about pneumococcal and other overwhelming post-splenectomy infections (OPSI) as the awareness of the patients about the risks of infection after splenectomy was poor. In particular, patients with splenectomy operation more than 10 years ago should be very careful about being asplenic as they were determined to have significantly lower level of vaccine-specific antibody production. Our study was also the first to show that splenectomy does not alter IgG avidity induced by pneumococcal vaccination.

Immune mechanisms in human Sarcoptes scabiei (Acari: Sarcoptidae) infestations.

Scabies is a parasitic infestation of human and animal skin caused by different strains of the itch mite, Sarcoptes scabiei. The World Health Organization (WHO) has declared scabies in human as a neglected tropical disease, and today over 200 million people worldwide are affected. The two most commonly reported clinical manifestation of the condition are ordinary (OS) and crusted scabies (CS). CS, which can lead to fatal consequences due to secondary bacterial infections, is mostly observed in immunocompromised subjects but can also, although rarely, be detected in immunocompetent individuals. Innate and adaptive immune system components are involved in protection and pathogenesis of scabies, although with some differences between OS and CS. While the cutaneous immune response is dominated by CD4+ T-cells in OS, it is mainly mediated by CD8+ T-cells in CS. The two clinical conditions also differ in CD4+ T-cell-mediated immune responses with mixed TH 1/TH 2 (protective) and TH 2/TH 17 (non-protective) immunoprofiles in OS and CS, respectively. Moreover, the development of CS is associated with early immunosuppression that is followed by deleterious immune response to uncontrolled mite proliferation. However, the immune response to scabies still needs further attention due to inconsistent results in the literature. The aim of this study is to attract more attention to this area by summarizing the current literature on innate and adaptive immune responses triggered against S. scabiei mites.

Altered tonsillar toll-like receptor (TLR)-1 and TLR-2 expression levels between periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA), and group A beta-hemolytic streptococcal (GAßHS) recurrent tonsillitis patients.

INTRODUCTION: Tonsillar microenvironment is thought to contribute to innate immune dysregulation responsible for the periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) because of beneficial effects of tonsillectomy on treatment of the syndrome. Accordingly previous studies reported altered lymphocyte frequency, cytokine level and microbial composition in PFAPA tonsils. The aim of our study is to monitor expression levels of pro-inflammatory cell surface Toll-like receptors (TLRs) which have important role in induction of inflammation and maintaining tissue haemostasis. MATERIALS AND METHODS: Seven patients with PFAPA syndrome, and eight patients with group A beta-hemolytic streptococcal (GAßHS) recurrent tonsillitis were included in our study. Tonsillar expression levels of TLR-1, -2, -4, -5, and -6 were monitored by immunohistochemistry (IHC). Expression levels were scored using semi-quantitative analysis method and were statistically analyzed by Two-Way Repeated Measures Analysis of Variance test. RESULTS: IHC analysis demonstrated expression of all TLRs in tonsillar surface epithelium (SE) and lymphoid interior (LI) except for TLR-6 which was not present in the former. There has not been any statistically significant difference in TLR expression levels between PFAPA and GAßHS tonsils, except for TLR-1 and TLR-2 which were higher on LI and lower on SE of PFAPA tonsils, respectively, than that of the GAßHS samples. CONCLUSIONS: Altered TLR expression levels may be involved in PFAPA pathogenesis. Future studies with higher patient number, uninflamed tonsils and cellular markers are required to further enlighten the role of TLRs in the development of syndrome.

Serological screening of West Nile virus among blood donors in northern Cyprus.

BACKGROUND: West Nile virus (WNV) is a neurotropic arbovirus that can also be transmitted through blood transfusion. Even though its geographic distribution has been expanding, there has not yet been any epidemiological data on WNV in northern Cyprus. The aim of our study is to fill this gap by using donated blood samples. METHODS: Samples collected from the main government hospital blood bank in Nicosia were analyzed by anti-WNV enzyme-linked immunosorbent assay (ELISA) (immunoglobulin M [IgM] and immunoglobulin G [IgG]). Seropositive samples were subjected to plaque reduction neutralization test (PRNT) for confirmation and analyzed by ELISA IgG avidity test and reverse transcription real-time polymerase chain reaction (rRT-PCR). RESULTS: Of the 760 sera samples, 2 (0.3%) were IgM+ and 31 (4.1%) were IgG+. Neutralization activity was detected in none (0.0%) of the IgM+ and 26 (83.9%) of IgG+ donor specimens. ELISA IgG avidity test reported high avidity in 21 (67.7%) and low avidity in one (3.2%) IgG+ sample. PRNT-confirmed anti-WNV IgG+ samples exhibited only borderline (19.2%) or high avidity (80.8%) values. rRT-PCR results were negative for both IgM+ and IgG+ samples. CONCLUSION: Anti-WNV antibodies were detected in northern Cyprus among blood donors. The establishment of preventive measures and evaluation of the geographic extent of the WNV in northern Cyprus are highly recommended.

Immune mechanisms in human and canine demodicosis: A review.

Demodex mites are saprophytic parasites of the mammalian skin, mostly found in or near pilosebaceous units of hairy regions. While they can be found in healthy humans and animals without causing any clinical manifestations, they were suggested to create pathogenic symptoms when they appear in high densities under favourable conditions (ie, demodicosis). Nevertheless, their role as the primary causative agent of the pathogenic conditions in humans is debated today. Canine demodicosis, which is highly prevalent in certain dog breeds, provides a valuable tool for studying the pathogenesis of human demodicosis. Canine and human demodicosis are caused by different Demodex species, and the clinical manifestations in former could be life-threatening. Nevertheless, current literature suggests similar immune responses and immune evasion mechanisms in human and canine demodicosis; cellular immunity appeared to have a central role in protection against demodicosis, and Demodex mites were shown to influence both innate and adaptive immune response to escape immune attack. The aim of this review is to summarize the relevant literature on demodicosis obtained from studies conducted on both organisms, and draw the attention to the effect of mite-associated factors (eg, microbiota) on the different clinical manifestations displayed during human and canine demodicosis.

Extended-spectrum ß-lactamase, plasmid-mediated AmpC ß-lactamase, fluoroquinolone resistance, and decreased susceptibility to carbapenems in Enterobacteriaceae: fecal carriage rates and associated risk factors in the community of Northern Cyprus.

Background: Antibiotic-resistant Enterobacteriaceae in the gastrointestinal flora can lead to infections with limited therapeutic options. Also, the resistant bacteria can be transferred from colonized persons to others. The present study was conducted to search the fecal carriage rates of (i) Enterobacteriaceae that produce extended-spectrum ß-lactamase (ESBL-E) and/or (ii) plasmid-mediated AmpC ß-lactamase (pAmpC-E), (iii) ciprofloxacin-resistant Enterobacteriaceae (CIP-RE), and (iv) carbapenem-intermediate or -resistant Enterobacteriaceae (CIRE) in Northern Cyprus. Methods: A total of 500 community-dwellers were recruited from consecutive admissions to the clinical laboratories of four hospitals. One rectal swab or stool sample was collected from each participant. A questionnaire was applied to evaluate possible risk factors associated with intestinal colonization of resistant bacteria. The samples were cultured on antibiotic containing media to screen for resistant bacteria colonization. The bacterial colonies that grew on the plates were subjected to further phenotypic tests to confirm the resistance. Results: Of 500 volunteers, ESBL-E, pAmpC-E, CIP-RE and CIRE carriage were detected in 107 (21.4%), 15 (3.0%), 51 (10.2%) and six (1.2%) participants, respectively. Escherichia coli was the most commonly recovered species among Enterobacteriaceae isolates. A significant proportion of ESBL-producing E. coli isolates (n = 22/107; 20.6%) was found to be co-resistant to CIP (p = 0.000, OR 3.21, 95% CI 1.76-5.87). In this study, higher socioeconomic status (CIP-RE: p = 0.024, OR 1.96, 95% CI 1.09-3.53), presence of gastrointestinal symptoms (CIRE: p = 0.033; OR 6.79, 95% CI 1.34-34.39), antibiotic use (ESBL-E: p = 0.031; OR 1.67, 95% CI 1.04-2.67; and CIRE: p = 0.033; OR 6.40, 95% CI 1.16-35.39), and travelling abroad (pAmpC-E: p = 0.010; OR 4.12, 95% CI 1.45-11.66) were indentified as risk factors. Conclusion: The study indicates that resistant Enterobacteriaceae isolates are carried by humans in the community. To prevent further spread of resistance, rational use of antibiotics should be encouraged, and antibiotic resistance should be carefully monitored in Northern Cyprus.

Skin-homing T-cell responses associated with Demodex infestation and rosacea.

AIMS: Our aim was to investigate the skin-homing T-cell immune responses triggered in patients with Demodex infestation and/or rosacea. METHODS: Collected whole blood samples were divided into four groups: control subjects; nonrosacea patients with Demodex infestation (Demodex group); papulopustular rosacea (PPR) patients without Demodex infestation (Rosacea group); and PPR patients with Demodex infestation (Rosacea/Demodex group). Following ex vivo activation, skin-homing CLA+CD4+ T-cell subset levels were monitored by flow cytometry. RESULTS: When compared with control subjects, among skin-homing CD4+ T-cell subsets analysed, Demodex patients had higher TH 9 and Treg cell levels; Rosacea subjects displayed elevated TH 1 cell levels; and Rosacea/Demodex patients exhibited increased frequencies of TH 9 and TH 22 cells. In contrast to Rosacea subjects, Rosacea/Demodex group members displayed higher TH 2 cell levels; and when compared with Demodex groups, they had higher TH 1 and TH 2 but lower Treg cell levels. Demodex group members also exhibited higher Treg but lower TH 1 and TH 22 levels than Rosacea/Demodex group subjects. CONCLUSIONS: The skin-homing T-cell responses associated with Demodex infestation and rosacea formation seem to influence each other. The present as well as future studies could contribute to the development of effective treatment strategies for demodicosis and rosacea.

Tonsillar antimicrobial peptide (AMP) expression profiles of periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) patients.

INTRODUCTION: PFAPA (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis) is the most frequent non-infectious cause of high fever observed among the European child population. While its cause is still not yet fully identified, PFAPA patients were previously shown to have altered tonsillar microbiome composition. Our study hypothesized that this is associated with a change in antimicrobial peptide (AMP) expression levels, as in the case of Crohn's disease which is another autoinflammatory disorder. METHODS AND MATERIALS: The tonsil specimens were isolated from seven patients with PFAPA syndrome, and six patients with group A beta-hemolytic streptococcal (GAßHS) recurrent tonsillitis. Tonsillar expression levels of human beta-defensin 1-2, cathelicidin, ribonuclease-7, and liver expressed antimicrobial peptide-1 were monitored by immunohistochemistry (IHC). Expression levels were scored using semi-quantitative analysis method and were statistically analyzed by Two-Way Repeated Measures Analysis of Variance test. RESULTS: Our results showed no significant difference in AMP expression levels between PFAPA and GAßHS patients. Immunolocalization of human beta-defensin 1 was different between the two groups; expressed at higher levels on tonsil surface epithelium (SE) than lymphoid interior (LI) in PFAPA patient group, while this was not evident in GAßHS patients group. CONCLUSIONS: Our results suggest that, PFAPA patients may be associated with altered AMP expression as in other autoinflammatory diseases. Future studies with subjects without any inflammatory condition are required for more precise conclusions.

The role of Treg population in pathogenesis of Crimean Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever (CCHF) is a severe human infection caused by CCHF virus (CCHFV). Today, although the literature on CCHF pathogenesis is still limited, it is thought to be associated with immunosuppression in the early phase of infection followed by pro-inflammatory immune response that may lead to fatal outcomes. The aim of this study is to investigate the role of regulatory T-cells (Treg cells) in the pathogenesis of CCHFV. Peripheral blood mononuclear cell samples collected from 14 acute CCHF patients with mild disease course and 13 healthy subjects were included in this study. Treg expression and functional levels were analyzed by flow cytometry. Treg cells were identified as CD4+CD25 + CD127dim cells, and their functional levels were compared by measuring their ability to suppress CD69 and CD154 expression by activated T-cells. The flow cytometry analysis revealed that total T-cell and helper T-cell levels did not vary between the two groups. In contrast, CCHF patients displayed higher Treg cell levels but lower Treg suppressive activities when compared with control subjects. This is the first study on the involvement of Treg cells in CCHF pathogenesis. Our results indicate that even though Treg cell levels are elevated during acute phase of CCHF infection, not all generated Treg cells has immunosuppressive capacity, and therefore may not represent 'true' Treg cell population. Future studies on the intrinsic mechanisms responsible for the reduced Treg inhibitory activities are required for further enlightening the CCHF pathogenesis, especially in the acute phase of the disease.

The effect of splenectomy on the levels of PCV-13-induced memory B- and T cells.

AIM: Splenectomised patients are associated with lifelong risk of fatal overwhelming post-splenectomy infection (OPSI), which is mostly caused by Streptococcus pneumoniae. Today OPSI cases can still be reported even in patients with appropriate vaccination. In our study, the levels of vaccine-specific memory B- and T cells were compared between control and splenectomised patients to enlighten the underlying reason. MATERIALS AND METHODS: Five healthy and 14 post-traumatic splenectomised individuals were vaccinated with 13-valent pneumococcal conjugate vaccine (PCV-13) followed by 23-valent pneumococcal polysaccharide vaccine (PPV-23). The levels of memory B- and T cells were compared by ELISPOT analysis. RESULTS: Splenectomised patients generated reduced levels of memory IgG B cells in response to PCV-13 vaccination, while the memory IFN-γ T-cell levels were undetectable in asplenic patients. This was despite the detection of vaccine-induced memory T-cell levels in control patients, which were analysed simultaneously following the same experimental protocol. CONCLUSION: Our results suggest that spleen is important, but not essential, for survival and/or generation of memory IgG B cells. In contrast, it seems to be indispensable for PCV-13-specific memory TH 1-cell levels. Studies enhancing the levels of vaccine-induced memory cells and further enlightening the immune responses in asplenic individuals are required to develop more effective vaccination strategies against OPSI.

Anti-Pneumococcal Vaccine-Induced Cellular Immune Responses in Post-Traumatic Splenectomized Individuals.

PURPOSE: Splenectomy is associated with increased risk of overwhelming post-splenectomy infections despite proper anti-pneumococcal vaccination. As most studies concentrated on vaccination-induced humoral immunity, the cellular immune responses triggered in splenectomized patients are not yet well studied. The present study aims to investigate this area as it can contribute to the development of more effective vaccination strategies. METHODS: Five healthy and 14 splenectomized patients were vaccinated with pneumococcal conjugate polysaccharide vaccine (PCV) followed by pneumococcal polysaccharide vaccine according to the guidelines established by Advisory Committee on Immunization Practices. PBMC samples collected 0, 8, and 12 weeks after PCV immunization were in vitro stimulated with PCV. Levels of lymphoproliferation, TH cell differentiation, and cytokine release were assessed by carboxyfluorescein succinimidyl ester labeling, intracellular cytokine staining, and ELISA, respectively. RESULTS: While TH1-dominated immune response was detected in both groups, asplenic individuals generated significantly lower levels of TH1 cells following in vitro stimulation. Similarly, levels of IFN-γ, IL-4, and IL-17 release and lymphoproliferation were significantly lower in asplenic patients. CONCLUSIONS: According to our data, splenectomy negatively influences the levels of PCV-induced lymphoproliferation, TH1 differentiation, and cytokine release. Besides, PCV failed to induce TH17-dominant immune response which is crucial for protection against extracellular pathogens.

Fungal recognition enhances mannose receptor shedding through dectin-1 engagement.

The mannose receptor (MR) is an endocytic type I membrane molecule with a broad ligand specificity that is involved in both hemostasis and pathogen recognition. Membrane-anchored MR is cleaved by a metalloproteinase into functional soluble MR (sMR) composed of the extracellular domains of intact MR. Although sMR production was initially considered a constitutive process, enhanced MR shedding has been observed in response to the fungal pathogen Pneumocystis carinii. In this work, we have investigated the mechanism mediating enhanced MR shedding in response to fungi. We show that other fungal species, including Candida albicans and Aspergillus fumigatus, together with zymosan, a preparation of the cell wall of Saccharomyces cerevisiae, mimic the effect of P. carinii on sMR production and that this effect takes place mainly through ß-glucan recognition. Additionally, we demonstrate that MR cleavage in response to C. albicans and bioactive particulate ß-glucan requires expression of dectin-1. Our data, obtained using specific inhibitors, are consistent with the canonical Syk-mediated pathway triggered by dectin-1 being mainly responsible for inducing MR shedding, with Raf-1 being partially involved. As in the case of steady-state conditions, MR shedding in response to C. albicans and ß-glucan particles requires metalloprotease activity. The induction of MR shedding by dectin-1 has clear implications for the role of MR in fungal recognition, as sMR was previously shown to retain the ability to bind fungal pathogens and can interact with numerous host molecules, including lysosomal hydrolases. Thus, MR cleavage could also impact on the magnitude of inflammation during fungal infection.

Influence of the mannose receptor in host immune responses.

Mannose receptor (MR) is a C-type lectin primarily expressed by macrophages and dendritic cells. Its three distinct extracellular binding sites recognise a wide range of both endogenous and exogenous ligands, therefore MR has been implicated in both homeostatic processes and pathogen recognition. However, the function of MR in host defence is not yet clearly understood as MR-deficient animals do not display enhanced susceptibility to pathogens bearing MR ligands. This scenario is even more complex when considering the role of MR in innate immune activation as, even though no intracellular signalling motif has been identified at its cytoplasmic tail, MR has been shown to be essential for cytokine production, both pro-inflammatory and anti-inflammatory. Furthermore, MR might interact with other canonical pattern recognition receptors in order to mediate intracellular signalling. In this review, we have summarised recent observations relating to MR function in immune responses and focused on its participation in phagocytosis, antigen processing and presentation, cell migration and intracellular signalling.