ABSTRACT
BACKGROUND: Scavenger receptor CD163 is exclusively expressed on monocytes/macrophages and is widely used as a marker for alternatively activated macrophages. However, the role of CD163 is not yet clear. OBJECTIVES: We sought to examine the function of CD163 in steady-state as well as in sterile and infectious inflammation. METHODS: Expression of CD163 was analyzed under normal and inflammatory conditions in mice. Functional relevance of CD163 was investigated in models of inflammation in wild-type and CD163-/- mice. RESULTS: We describe a subpopulation of bone marrow-resident macrophages (BMRMs) characterized by a high expression of CD163 and functionally distinct from classical bone marrow-derived macrophages. Development of CD163+ BMRMs is strictly dependent on IFN regulatory factor-8. CD163+ BMRMs show a specific transcriptome and cytokine secretion pattern demonstrating a specific immunomodulatory profile of these cells. Accordingly, CD163-/- mice show a stronger inflammation in allergic contact dermatitis, indicating a regulatory role of CD163. However, CD163-/- mice are highly susceptible to S aureus infections, demonstrating the relevance of CD163 for antimicrobial defense as well. CONCLUSIONS: Our data indicate that anti-inflammatory and immunosuppressive mechanisms are not necessarily associated with a decreased antimicrobial activity. In contrast, our data define a novel macrophage population that controls overwhelming inflammation on one hand but is also necessary for an effective control of infections on the other hand.
Subject(s)
Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Bone Marrow Cells/metabolism , Dermatitis, Allergic Contact/immunology , Inflammation/immunology , Macrophages/metabolism , Receptors, Cell Surface/metabolism , Staphylococcal Infections/immunology , Staphylococcus aureus/physiology , Animals , Antigens, CD/genetics , Antigens, Differentiation, Myelomonocytic/genetics , Bone Marrow Cells/immunology , Cells, Cultured , Cytokines/metabolism , Disease Models, Animal , Disease Susceptibility , Humans , Immunomodulation , Interferon Regulatory Factors/genetics , Interferon Regulatory Factors/metabolism , Macrophage Activation , Macrophages/immunology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Receptors, Cell Surface/genetics , TranscriptomeABSTRACT
PATIENT PRESENTATION: We report the case of a 66 year old female who presented to our institution fourteen years after receiving a St. Jude Mechanical Mitral Valve Replacement. She presented in refractory NYHA class IV congestive heart failure with comorbidities of acute renal failure, liver failure, and mental status changes. She was found to have immobility of one of the mitral valve disks with resultant severe mitral stenosis with a mean pressure gradient of 12 mmHg. EVALUATION AND MANAGEMENT: The patient was found to have an STS predicted mortality of 39% with redo surgical MVR, and evaluation by the valve team led to a recommendation of a hybrid surgical and transcatheter procedure. The patient underwent femoral bypass and hypothermia with a sternotomy and left atrial approach. The mechanical discs were removed utilizing needle drivers without removal of the St. Jude ring. Subsequently, a 26 mm Edwards Sapien XT valve was deployed under direct and fluoroscopic visualization. The patient had an event free post-operative course, and one year following the procedure has had an outstanding clinical response with NYHA class II congestive heart failure. Her echocardiogram reveals normal valve function with a MPG of 4 mmHg without mitral regurgitation. CONCLUSION: Transatrial hybrid TMVR within the ring of a St. Jude mechanical mitral valve appears to be a feasible procedure which may be used in the future to decrease morbidity and mortality associated with high-risk redo-MVR in patients with mechanical mitral valve prostheses.
