NK Cells and Trophoblasts: Partners in Pregnancy

In placental mammals, viviparity—the production of living young within the mother's body—evolved under the auspices of the immune system. Elements of immunity were incorporated, giving pregnancy a mildly inflammatory character. Formation of the placenta, the organ that feeds the fetus, involves a cooperation between maternal natural killer (NK) cells and fetal trophoblast cells that remodels the blood supply. Recent research reveals that this process and human reproductive success are influenced by polymorphic HLA-C ligands and their killer cell immunoglobulin-like receptors (KIR)

Staphylococcus aureus Small Colony Variants in Prosthetic Joint Infection

Background. Small colony variants of Staphylococcus aureus tend to persist despite antimicrobial therapy, especially when involved in implant-associated infections. Methods. We analyzed 5 cases of hip prosthesis-associated infections due to small colony variants, including their course prior to identification of the pathogen. Biopsy investigations included microbiological examination and, in 1 case, transmission electron microscopy to detect intracellular bacteria in nonprofessional phagocytes. A treatment concept was elaborated on the basis of a published algorithm and patients were managed accordingly. Results. The patients' mean age was 62.2 years. All patients experienced treatment failures prior to isolation of small colony variants, despite as many as 3 surgical revisions and up to 22 months of antibiotics. Transmission electron microscopy performed on biopsy specimens from periprosthetic tissue revealed intracellular cocci in fibroblasts. All prostheses were removed without implanting a spacer, and antimicrobial agents were administered for 5.5-7 weeks. Reimplantation of the prosthesis was performed for 4 patients. Follow-ups were uneventful in all 5 cases. Conclusions. In the case of a poor response to adequate antimicrobial and surgical treatment in implant-associated staphylococcal infections, small colony variants should be considered and actively sought. In our case series, a 2-stage exchange without implantation of a spacer combined with antimicrobial therapy for an implant-free interval of 6-8 weeks was associated with successful outcome, with a mean follow-up of 24 month

Propionibacterium spp. in prosthetic joint infections: a diagnostic challenge

Introduction: Propionibacterium species are common inhabitants of the skin and usually non-pathogenic for humans. However, Propionibacterium spp. can occasionally cause infections, but are estimated to play a minor role in prosthetic joint infections (PJI). The relative frequency of these anaerobes and their potential to cause surgical site infection may be clinically underestimated. An unknown proportion of these infections might be missed, since little is known about their clinical presentation, and since growth of Propionibacterium spp. in diagnostic samples is often interpreted as contamination. Thus, a hypothesis is being tested, stating that Propionibacterium spp. is not as rare as often reported, and it can cause severe soft-tissue damages in PJI. Materials and methods: In this retrospective analysis, we reviewed all PJI that had been treated in our institution from 2000 to 2005, and assessed the relative frequency of those caused by Propionibacterium spp. In the identified cases, features that led to the diagnosis (clinical, laboratory, radiological, microbiological and histopathological characteristics) were analysed. Results: Of 139 cases of prosthetic joint infections, 8(6%) were caused by Propionibacterium spp. Seven patients complained of pain as the main symptom, and four had damaged soft-tissue. Analysis of the diagnostic procedures showed a median of 39% positive samples out of all cultured biopsies (median 9.5 biopsies per case), with a median time-to-positivity of 8days. Results of histopathological examinations of the periprosthetic tissue correlated well with the clinical courses. Conclusions: Our data suggest that Propionibacterium associated prosthetic joint infections occur at a relative frequency that is comparable to many other pathogens. Clinical signs are generally subtle, but the spectrum includes also significant soft-tissue damages. In this study, a median of 9.5 biopsies per case, an incubation time of 14days, and the aid of histopathological examinations proved to be helpful in establishing the diagnosi

Killer Cell Immunoglobulin-like Receptor Workshop: Insights into Evolution, Genetics, Function, and Translation

The seventh killer cell immunoglobulin-like receptor (KIR) workshop was held at Tammsvik, Stockholm, Sweden, in the summer of 2011. This intimate and isolated setting brought together approximately 100 investigators, from a range of scientific disciplines, who are all actively working on KIRs in humans or closely related primate species

Killer Cell Inhibitory Receptor Recognition of Human Leukocyte Antigen (HLA) Class I Blocks Formation of a pp36/PLC-γ Signaling Complex in Human Natural Killer (NK) Cells

The killer cell inhibitory receptors (KIR) of human natural killer (NK) cells recognize human leukocyte antigen class I molecules and inhibit NK cell cytotoxicity through their interaction with protein tyrosine phosphatases (PTP). Here, we report that KIR recognition of class I ligands inhibits distal signaling events and ultimately NK cell cytotoxicity by blocking the association of an adaptor protein (pp36) with phospholipase C-γ in NK cells. In addition, we demonstrate that pp36 can serve as a substrate in vitro for the KIR-associated PTP, PTP-1C (also called SHP-1), and that recognition of class I partially disrupts tyrosine phosphorylation of NK cell proteins, providing evidence for KIR-induced phosphatase activity

Short KIR Haplotypes in Pygmy Chimpanzee (Bonobo) Resemble the Conserved Framework of Diverse Human KIR Haplotypes

Some pygmy chimpanzees (also called Bonobos) give much simpler patterns of hybridization on Southern blotting with killer cell immunoglobulin-like receptor (KIR) cDNA probes than do either humans or common chimpanzees. Characterization of KIRs from pygmy chimpanzees having simple and complex banding patterns identified nine different KIRs, representing seven genes. Five of these genes have orthologs in the common chimpanzee, and three of them (KIRCI, KIR2DL4, and KIR2DL5) also have human orthologs. The remaining two genes are KIR3D paralogous to the human and common chimpanzee major histocompatibility complex A– and/or -B–specific KIRs. Within a pygmy chimpanzee family, KIR haplotypes were defined. Simple patterns on Southern blot were due to inheritance of “short” KIR haplotypes containing only three KIR genes, KIRCI, KIR2DL4, and KIR3D, each of which represents one of the three major KIR lineages. These three genes in pygmy chimpanzees or their corresponding genes in humans and common chimpanzees form the conserved “framework” common to all KIR haplotypes in these species and upon which haplotypic diversity is built. The fecundity and health of individual pygmy chimpanzees who are homozygotes for short KIR haplotypes attest to the viability of short KIR haplotypes, indicating that they can provide minimal, essential KIRs for the natural killer and T cells of the hominoid immune system