Showing papers by "Frederic Geissmann published in 2008"
TL;DR: The potential roles of monocytes in the immune response, the existence of functional subsets and their relationship with other myeloid cells, including dendritic cells are discussed.
Abstract: Monocytes can have important effects on the polarization and expansion of lymphocytes and may contribute to shaping primary and memory T-cell responses in humans and mice. However, their precise contribution in terms of cellular subsets and the molecular mechanisms involved remains to be determined. Mouse monocytes originate from a bone marrow progenitor, the macrophage and DC precursor (MDP), which also gives rise to conventional dendritic cells through a separate differentiation pathway. Mouse monocytes may be grouped in different functional subsets. The CD115(+) Gr1(+) 'inflammatory' monocyte subset can give rise not only to immunostimulatory 'TipDCs' in infected mice but also to immunosuppressive 'myeloid-derived suppressor cells' in tumor-bearing mice. CD115(+) Gr1(+) monocytes can also contribute to the renewal of several resident subsets of macrophages and DCs, such as microglia and Langerhans cells, in inflammatory conditions. The CD115(+) Gr1(-) 'resident' monocyte subset patrols blood vessels in the steady state and extravasates during infection with Listeria monocytogenes or in the healing myocardium. CD115(+) Gr1(-) monocytes are responsible for an early and transient inflammatory burst during Lm infection, which may play a role in the recruitment of other effector cells and subsequently differentiate toward 'M2'-like macrophages that may be involved in wound healing. More research will no doubt confirm the existence of more functional subsets, the developmental relationship between mouse subsets as well as the correspondence between mouse subsets and human subsets of monocytes. We will discuss here the potential roles of monocytes in the immune response, the existence of functional subsets and their relationship with other myeloid cells, including dendritic cells.
416 citations
TL;DR: The findings do not support the hypothesis of a role of EBV, CMV, or HHV-6 in the pathogenesis of LCH, and indicate that the frequent detection of Epstein-barr virus (EBV) in Langerhans cell histiocytosis is accounted for by the infection of bystander B lymphocytes in LCH granuloma.
Abstract: Background Langerhans cell histiocytosis (LCH) is a rare disease that affects mainly young children, and which features granulomas containing Langerhans-type dendritic cells. The role of several human herpesviruses (HHV) in the pathogenesis of LCH was suggested by numerous reports but remains debated. Epstein-barr virus (EBV, HHV-4), & Cytomegalovirus (CMV, HHV-5) can infect Langerhans cells, and EBV, CMV and HHV-6 have been proposed to be associated with LCH based on the detection of these viruses in clinical samples. Methodology We have investigated the prevalence of EBV, CMV and HHV-6 infection, the characters of antibody response and the plasma viral load in a cohort of 83 patients and 236 age-matched controls, and the presence and cellular localization of the viruses in LCH tissue samples from 19 patients. Principal Findings The results show that prevalence, serological titers, and viral load for EBV, CMV and HHV-6 did not differ between patients and controls. EBV was found by PCR in tumoral sample from 3/19 patients, however, EBV small RNAs EBERs –when positive-, were detected by in situ double staining in bystander B CD20+ CD79a+ lymphocytes and not in CD1a+ LC. HHV-6 genome was detected in the biopsies of 5/19 patients with low copy number and viral Ag could not be detected in biopsies. CMV was not detected by PCR in this series. Conclusions/Significance Therefore, our findings do not support the hypothesis of a role of EBV, CMV, or HHV-6 in the pathogenesis of LCH, and indicate that the frequent detection of Epstein-barr virus (EBV) in Langerhans cell histiocytosis is accounted for by the infection of bystander B lymphocytes in LCH granuloma. The latter observation can be attributed to the immunosuppressive micro environment found in LCH granuloma.
62 citations
TL;DR: It is demonstrated that LCMV‐infected Rab27a‐deficient C57BL/6 mice develop features consistent with HLH and, therefore, represent a murine model of HLH in human Griscelli syndrome type 2.
Abstract: Griscelli syndrome type 2 is caused by mutations in the RAB27A gene and is a rare and potentially fatal immune disorder associated with hemophagocytic lymphohistiocytosis (HLH). Animal models could provide assistance for better understanding the mechanisms and finding new treatments. Rab27a-deficient (ashen) mice do not spontaneously develop HLH. When injected with lymphocytic choriomeningitis virus (LCMV) strain WE, Rab27a-deficient C57BL/6 mice developed wasting disease, hypothermia, splenomegaly, cytopenia (anemia, neutropenia and thrombocytopenia), hypertriglyceridemia and increased levels of IFN-gamma, TNF-alpha, GM-CSF, IL-12, CCL5 and IL-10. Activated macrophages with hemophagocytosis were found in liver sections of these mice. Compared with perforin-deficient mice, LCMV-infected Rab27a-deficient mice showed a substantially better survival rate and slightly higher viral doses were needed to trigger HLH in Rab27a-deficient mice. This study demonstrates that LCMV-infected Rab27a-deficient C57BL/6 mice develop features consistent with HLH and, therefore, represent a murine model of HLH in human Griscelli syndrome type 2.
56 citations
TL;DR: A new study finds that local homeostatic expansion of conventional dendritic cells in the spleen is regulated by Fms-related tyrosine kinase-3 ligand.
Abstract: A new study finds that local homeostatic expansion of conventional dendritic cells in the spleen is regulated by Fms-related tyrosine kinase-3 ligand.
20 citations