NOD-Like Receptors in Infection, Immunity, and Diseases

Nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) are pattern-recognition receptors similar to toll-like receptors (TLRs). While TLRs are transmembrane receptors, NLRs are cytoplasmic receptors that play a crucial role in the innate immune response by recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Based on their N-terminal domain, NLRs are divided into four subfamilies: NLRA, NLRB, NLRC, and NLRP. NLRs can also be divided into four broad functional categories: inflammasome assembly, signaling transduction, transcription activation, and autophagy. In addition to recognizing PAMPs and DAMPs, NLRs act as a key regulator of apoptosis and early development. Therefore, there are significant associations between NLRs and various diseases related to infection and immunity. NLR studies have recently begun to unveil the roles of NLRs in diseases such as gout, cryopyrin-associated periodic fever syndromes, and Crohn's disease. As these new associations between NRLs and diseases may improve our understanding of disease pathogenesis and lead to new approaches for the prevention and treatment of such diseases, NLRs are becoming increasingly relevant to clinicians. In this review, we provide a concise overview of NLRs and their role in infection, immunity, and disease, particularly from clinical perspectives.

Indirect Effects of Pneumococcal Conjugate Vaccines in National Immunization Programs for Children on Adult Pneumococcal Disease

The pneumococcal conjugate vaccine (PCV) was developed to overcome the limitations of the pneumococcal polysaccharide vaccine, which produces poor immunogenicity in infants younger than 2 years. As many countries have included PCVs in national immunization programs for children, the incidence of invasive pneumococcal disease caused by vaccine type Streptococcus pneumoniae has declined markedly, not only among the vaccinated pediatric population, but also among unvaccinated adults. In this review, we present a concise overview of the indirect effects of mass pediatric PCV immunization on unvaccinated adults.

Diagnosis of Pneumococcal Pneumonia: Current Pitfalls and the Way Forward

Streptococcus pneumoniae is the most common cause of community-acquired pneumonia. However, it can also asymptomatically colonize the upper respiratory tract. Because of the need to distinguish between S. pneumoniae that is simply colonizing the upper respiratory tract and S. pneumoniae that is causing pneumonia, accurate diagnosis of pneumococcal pneumonia is a challenging issue that still needs to be solved. Sputum Gram stains and culture are the first diagnostic step for identifying pneumococcal pneumonia and provide information on antibiotic susceptibility. However, these conventional methods are relatively slow and insensitive and show limited specificity. In the past decade, new diagnostic tools have been developed, particularly antigen (teichoic acid and capsular polysaccharides) and nucleic acid (ply, lytA, and Spn9802) detection assays. Use of the pneumococcal antigen detection methods along with biomarkers (C-reactive protein and procalcitonin) may enhance the specificity of diagnosis for pneumococcal pneumonia. This article provides an overview of current methods of diagnosing pneumococcal pneumonia and discusses new and future test methods that may provide the way forward for improving its diagnosis.

Clinical Implications of Pneumococcal Serotypes: Invasive Disease Potential, Clinical Presentations, and Antibiotic Resistance

Streptococcus pneumoniae can asymptomatically colonize the nasopharynx and cause a diverse range of illnesses. This clinical spectrum from colonization to invasive pneumococcal disease (IPD) appears to depend on the pneumococcal capsular serotype rather than the genetic background. According to a literature review, serotypes 1, 4, 5, 7F, 8, 12F, 14, 18C, and 19A are more likely to cause IPD. Although serotypes 1 and 19A are the predominant causes of invasive pneumococcal pneumonia, serotype 14 remains one of the most common etiologic agents of non-bacteremic pneumonia in adults, even after 7-valent pneumococcal conjugate vaccine (PCV7) introduction. Serotypes 1, 3, and 19A pneumococci are likely to cause empyema and hemolytic uremic syndrome. Serotype 1 pneumococcal meningitis is prevalent in the African meningitis belt, with a high fatality rate. In contrast to the capsule type, genotype is more closely associated with antibiotic resistance. CC320/271 strains expressing serotype 19A are multidrug-resistant (MDR) and prevalent worldwide in the era of PCV7. Several clones of MDR serotype 6C pneumococci emerged, and a MDR 6D clone (ST282) has been identified in Korea. Since the pneumococcal epidemiology of capsule types varies geographically and temporally, a nationwide serosurveillance system is vital to establishing appropriate vaccination strategies for each country.

Nasopharyngeal Pneumococcal Carriage of Children Attending Day Care Centers in Korea: Comparison between Children Immunized with 7-valent Pneumococcal Conjugate Vaccine and Non-immunized

To confirm the effect of 7-valent pneumococcal conjugate vaccine (PCV7), pneumococcal nasopharyngeal (NP) carriage was compared between vaccinated (3 + 1 doses PCV7) and non-vaccinated children. Vaccinated subjects were recruited from highly vaccinated regions (> or = 60%), Seoul and Incheon whereas control subjects were recruited from Jeju Island where vaccination rates are low (< 15%). NP swabs were obtained from 400 children aged 18-59 months. Serotype and antibiotic susceptibility was analyzed. Pneumococcal carriage rate was 18.0% (36/200) and 31.5% (63/200) for the vaccinated and control group, respectively. Among those vaccinated, 41.7% (15/36) of the serotypes were vaccine-related type (VRT: 6A, 6C, 19A) with the most common serotype 6C. The next common type was non-typable/non-capsule 30.6% (11/36) followed by non-vaccine type 16.7% (6/36) and vaccine type (VT) serotypes were found in only 11.1% (4/36). In contrast, 52.4% (33/63) of the isolates in the control group were VT. Resistance rates for penicillin and erythromycin were lower in the vaccine group (vaccine vs control; penicillin 45.2% vs 71.4%, erythromycin 74.2% vs 90.5%, P < 0.05). Multi-drug resistance was also lower in vaccinated subjects (vaccine vs control; 45.2% vs 69.8%, P < 0.05). PCV7 reduces carriage in VT which leads to replacement of pneumococci by antibiotic susceptible VRT or non-vaccine type strains.

Enzyme Amplification, A Method Applied to Provide An ELISA for Studying Anti-Hib-Ps Antibodies in Children

PURPOSE: Enzyme immunoassay (EIA) is now a widely used technique. We have described the application of enzyme amplification (sensitive ELISA) in the field of immunoassays of pediatric population. There are two issues with the sensitive ELISA. First is that one can minimize the serum volume, an important concern for pediatricians. The second is the problem of background signal. We demonstrate that it is possible to develop EIAs of high sensitivity and detectability with using very small volume of infant's sera immunized with Hib-PRP vaccine. METHODS: Monoclonal Abs HG11, HP6016, HK2, and KL1 specific for human IgG1, IgG2, C , and C were used. The mAb OAK-1 specific for a subfamily of V I L chains (V Ia), the mAbs KB13 and B12 specific for human V II and V III L chains were also used respectively. Adults were immunized with Hib-CRM vaccine. Immune serum was obtained 4 to 8 wk after immunization. Twenty infants received Hib-CRM vaccine at 2, 4, and 6 month of age and blood samples were obtained at 7 month old. The amount of anti-Hib-PS Ab expressing a V subgroup or V was determined by sandwich type immunoassays using conventional substrate. The amount of the enzyme immobilized to the well was determined with para-nitrophenyl phosphate substrate. A standard ELISA was performed but different substrate (lyophilized NADPH) and amplifier (alcohol dehydrogenase and diaphorase) were used to develop color in final step for enzyme amplification method. RESULTS: We get the dose-response curves obtained using the conventional and amplified detection methods in the anti-PRP Ab assay. The sensitivities of the two assay methods were compared. We can increase the sensitivities four to sixteen folds and minimize the infant's sera volume to perform varing anti-PRP antibody assays. To obtain the advantages of increased sensitivity, any background is minimized by using noncontaminated reagents. CONCLUSIONS: It is possible to develop EIAs of high sensitivity and detectability with using very small volume of infant's sera with using enzyme amplification system (sensitive ELISA).

Structure and Expression of Human Antibody Clones Specific for H. influenzae type b Capsular Polysaccharides

No abstract available.