Significance Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are autoimmune diseases characterized by accumulation of myeloid cells in the central nervous system (CNS). Both harmful and beneficial myeloid cells are present in EAE/MS, and a goal of MS therapy is to preferentially remove harmful myeloid cells. The receptor for CSF-1 (CSF-1R) is found on myeloid cells and is important for their survival. CSF-1R can bind two ligands, CSF-1 and IL-34, but it is not known whether their functions in EAE/MS differ. We found that blocking CSF-1 depleted only harmful myeloid cells in the CNS and suppressed EAE, whereas blocking IL-34 had no effect. Thus, we propose that blocking CSF-1 could be a therapy for MS.

Introduction Mucormycosis following hematopoietic stem cell transplant (HSCT) carries a very high mortality rate. Pulmonary mucormycosis often leads to systemic dissemination and eventual death. It is imperative for transplant providers to have a high level of suspicion for mucormycosis and initiate early treatment. Here, we present a 64-year-old woman who died of disseminated mucormycosis 13 days following her allogeneic HSCT. Case Presentation A 64-year-old female with a history of acute myeloid leukemia (AML) presented for allogeneic HSCT and passed away from intracerebral hemorrhage secondary to mucormycosis infection 13 days following her transplant. On autopsy, it was found she had angioinvasive mucormycosis in her frontal lobe leading to cerebral edema which eventually led to tonsillar herniation and brainstem infarction. Her lungs were the likely source of infectious dissemination. Discussion This case represents an unusual course of events following HSCT in that no other published case shows tonsillar herniation resulting from mucormycosis-related intracerebral swelling. We also report this case because it is believed mucormycosis in HSCT patients is underreported. Additionally, our case highlights the importance of increased vigilance for mucormycosis in patients with prolonged neutropenia prior to HSCT and the potential link of voriconazole prophylaxis and increased risk for mucormycosis.

GATA-binding factor 1 (GATA1) is a transcription factor that governs the development and function of multiple hematopoietic cell lineages. GATA1 is expressed in hematopoietic stem and progenitor cells (HSPCs) and is essential for erythroid lineage commitment, but if and what role it has in hematopoietic stem cell (HSC) biology and in the development of myeloid lineage cells is less clear. We initially set out to test the role of eosinophils in experimental autoimmune encephalomyelitis (EAE), a model of CNS autoimmunity, by using ΔdblGATA mice, which lack eosinophils due to deletion of the dblGATA enhancer to Gata1 that alters its expression. ΔdblGATA mice were resistant to EAE, but not because of the lack of eosinophils, suggesting that these mice have an additional defect. ΔdblGATA mice with EAE had fewer inflammatory myeloid cells than control mice, suggesting that the resistance to EAE is caused by a defect in myeloid cells. Naïve ΔdblGATA mice also had reduced frequency of blood CD11b+ myeloid cells, indicating a defect in myeloid cell production. Examination of HSPCs revealed fewer HSCs and myeloid cell progenitors in ΔdblGATA bone marrow, and competitive bone marrow chimera experiments showed a reduced capacity of ΔdblGATA bone marrow to reconstitute immune cells, suggesting that reduced numbers of ΔdblGATA HSPCs causes a functional deficit during inflammation. Taken together, our data show that GATA1 regulates the number of HSPCs, and that reduced GATA1 expression, due to dblGATA deletion, results in a diminished immune response following inflammatory challenge.