How do macrophages detect viruses?
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| In this study, we show that influenza viruses differ markedly in their abilities to infect murine macrophages in vitro and that infection of macrophages is nonproductive and no infectious virus is released. | |
18 Citations | IMPORTANCE Our studies clearly demonstrate that there are substantial biological differences in the patterns of cellular gene expression between macrophages infected with different poxvirus strains and that these changes are due specifically to infection with the distinct viruses. |
18 Citations | Taken together, these results increase our understanding of how these viruses interact with human macrophages, at the cellular and molecular levels, and suggest mechanisms that may underlie their utility as recombinant vaccine vectors. |
| This suggests that virus might be shed from infected macrophages and then reinfect other macrophages. |
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How does macrophage develop from HSC?4 answersMacrophages develop from hematopoietic stem cells (HSCs) through a complex process influenced by various factors, including the microenvironment and specific signaling pathways. Initially, HSCs undergo differentiation into hematopoietic progenitor cells (HPCs), which can migrate from the bone marrow into circulation under stress conditions or in response to specific signals, such as those mediated by macrophages through the secretion of granulocyte colony-stimulating factor in a receptor for advanced glycation end products (RAGE) signaling-dependent manner. This mobilization is part of the body's response to immune challenges, wound repair, or tissue regeneration.
The differentiation of HSCs into macrophages can be directed in vitro by exposing hematopoietic stem and progenitor cells (HSPCs) to various pathogen-associated molecular patterns (PAMPs) and cytokines, such as GM-CSF, which drive the cells towards myeloid lineage differentiation. Toll-like receptor (TLR) agonists, for example, have been shown to influence the functional properties of the derived macrophages, including their cytokine production capabilities.
In addition to traditional differentiation pathways, recent studies have explored the generation of macrophages from induced pluripotent stem cells (iPSCs) and primary human HSPCs. iPSCs offer a scalable source of genetically identical and editable cells for macrophage production, while HSPCs have been successfully used to generate functional chimeric antigen receptor (CAR) macrophages targeting specific antigens in solid tumor therapy. These advancements highlight the potential of both iPSCs and HSPCs as sources for generating macrophages ex vivo for therapeutic purposes.
Furthermore, the development of macrophages from HSCs is marked by a transition through various precursor stages, including monoblasts, promonocytes, and monocytes, before differentiating into tissue-resident or exudate macrophages depending on the presence of inflammatory stimuli or growth factors like M-CSF and GM-CSF. This differentiation is also influenced by the microenvironment and the presence of specific cytokines, which can lead to the generation of macrophages with distinct phenotypes, such as the M1 or M2 subtypes, each playing unique roles in immune responses and tissue homeostasis.
In summary, the development of macrophages from HSCs is a multifaceted process that involves migration, differentiation, and maturation stages influenced by internal and external signals, including cytokines, growth factors, and the cellular microenvironment.
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