Dynamic regulation of leukocyte population size and activation state is crucial for an effective immune response. In malaria, Plasmodium parasites elicit robust host expansion of macrophages and monocytes, but the underlying mechanisms remain unclear. Here we show that myeloid expansion during P. chabaudi infection is dependent upon both CD4+ T cells and the cytokine Macrophage Colony Stimulating Factor (MCSF). Single-cell RNA-Seq analysis on antigen-experienced T cells revealed robust expression of Csf1, the gene encoding MCSF, in a sub-population of CD4+ T cells with distinct transcriptional and surface phenotypes. Selective deletion of Csf1 in CD4+ cells during P. chabaudi infection diminished proliferation and activation of certain myeloid subsets, most notably lymph node-resident CD169+ macrophages, and resulted in increased parasite burden and impaired recovery of infected mice. Depletion of CD169+ macrophages during infection also led to increased parasitemia and significant host mortality, confirming a previously unappreciated role for these cells in control of P. chabaudi. This work establishes the CD4+ T cell as a physiologically relevant source of MCSF in vivo; probes the complexity of the CD4+ T cell response during type 1 infection; and delineates a novel mechanism by which T helper cells regulate myeloid cells to limit growth of a blood-borne intracellular pathogen.
A reference is omitted from the first sentence of the third paragraph under the subheading "A role for MCSF-dependent CD169+ macrophages in control of P. chabaudi" in the Results section. The sentence should read: CD169+ macrophages have not previously been examined for involvement in control of P. chabaudi infection, but a recent study demonstrated that systemic depletion of CD169+ macrophages increased tissue sequestration of parasites, morbidity, and mortality in a model of experimental cerebral malaria (ECM) employing the pathogen P. berghei ANKA in ECM-resistant Balb/C mice (Gupta et al., 2016).
ResumoA terapia gênica utiliza técnicas de engenharia genética para interferir na origem de uma doença. Nesta técnica introduz-se uma sequência de DNA codificante nas células do paciente como tratamento para a correção de um problema recorrente devido a um gene mutado. O uso de vetores virais recombinantes para introduzir o gene correto no indivíduo tem se mostrado bastante desafiador e promissor. Este artigo tem como objetivo apresentar de forma atualizada os conceitos básicos e as perspectivas da terapia gênica para doenças as doenças: fibrose cística, artrite reumatoide, hemofilia e dislipidemia (deficiência da lipoproteína lipase) utilizando o vírus adeno-associado (VAA) como vetor doador do novo gene. Os avanços obtidos no emprego desta técnica, como método de tratamento, podem contribuir largamente para a otimização da terapêutica e, consequentemente, melhorar a qualidade de vida de pacientes portadores de diferentes doenças incuráveis. Neste sentido, os VAA têm se mostrado tecnologicamente versáteis, seguros e efetivos veículos no procedimento.Palavras-chave: terapia gênica, vírus adeno-associado, fibrose cística, artrite reumatóide, hemofilia, LPLD. AbstractGene therapy uses genetic engineering techniques to interfere with the origin of a disease. In this technique a DNA coding sequence is introduced into the patient's cells as treatment for the correction of a recurring problem due to a mutated gene. The use of recombinant viral vectors to introduce the correct gene into the patient has shown to be quite challenging and promising approach. This article aims to update the basic concepts and the perspectives of gene therapy for diseases such as cystic fibrosis, rheumatoid arthritis, hemophilia and dyslipidemia (lipoprotein lipase deficiency) using adenoassociated virus (AAV) as the donor vector of the new gene. The advances obtained with the use of this technique as a treatment can contribute greatly to the optimization of the therapy and, consequently, improve the life quality of patients with different incurable diseases. In this way, AAV has proven to be technologically versatile, safe and effective vehicles in the procedure.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.