The Functional Heterogeneity of Macrophages at the Single Cell Level

McIntrye, J; Rowley, D.; Jenkin, CR

doi:10.1038/icb.1967.67

Cited by 36 publications

(14 citation statements)

References 8 publications

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“…Microscopy and FACS revealed diverse phenotypes, including uninfected cells and cells infected with single or multiple, live (yellow) or dead (red) bacteria, as has been previously described (McIntrye et al, 1967) ( Figures 1B, 1C ). This variability is neither simply a transient phenomenon nor a mere outcome of the specific MOI chosen, since it is sustained throughout the 24 hour time course ( Figure S1B ) and with increasing MOI ( Figure S1C ).…”

Section: Resultssupporting

confidence: 72%

“…Indeed, infection of macrophages with Salmonella generates well-documented diverse outcomes: some macrophages engulf the bacteria, while others remain uninfected (McIntrye et al, 1967); some macrophages lyse the ingested bacteria, while others are permissive to intracellular bacterial survival (McIntrye et al, 1967); some macrophages will undergo cell death with bacterial release (Monack et al, 1996), while others survive and allow bacteria to multiply or persist intracellularly (Helaine et al, 2010). Despite longstanding observations of these diverse outcomes however, we currently lack an understanding of the underlying molecular mechanisms in either the host or pathogen.…”

Section: Introductionmentioning

confidence: 99%

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Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses

Avraham

Haseley

Brown

et al. 2015

Cell

286

263

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Summary Encounters between immune cells and invading bacteria ultimately determine the course of infection. These interactions are usually measured in populations of cells, masking cell-to-cell variation that may be important for infection outcome. To characterize gene expression variation that underlies distinct infection outcomes, we developed an experimental system that combines single-cell RNA-seq with fluorescent markers, monitoring infection phenotypes. Probing the responses of individual macrophages to invading Salmonella, we find that variation between individual infected host cells is determined by the heterogeneous activity of bacterial factors in individual infecting bacteria. We illustrate how variable PhoPQ activity in the population of invading bacteria drives variable host Type I IFN responses by modifying LPS in a subset of bacteria. This work demonstrates a causative link between host and bacterial variability, with cell-to-cell variation between different bacteria being sufficient to drive radically different host immune responses. This co-variation has implications for host-pathogen dynamics in vivo.

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Section: Resultssupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses

Avraham

Haseley

Brown

et al. 2015

Cell

286

263

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“…For technical reasons the anti-microbial potential of activated macrophages in vitro has been less extensively studied. McZntyre et al [85] found a wide variation in the bactericidal capacity of individual macrophages. In limited studies we have found that smaller macrophages, separated by sedimentation velocity, are somewhat more potent than larger cells in killing Salmonella enteritidis in vitro [54].…”

Section: Activationmentioning

confidence: 99%

Macrophage Heterogeneity

1979

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Macrophages are a mobile, functionally diverse group of cells which may be recruited and stimulated to a high degree of metabolic activity. Heterogeneity may be detected from one site to another and result from local influences, e.g. lung v. peritoneal cells, or occur within a population and arise dur to different stages of differentiation, maturation or activation or possibly from distinct cell lines. Recruitment and turnover are important determinants of the diversity of cells at any one site. In addition, anti-tumour, anti-microbial and secretory capacities of macrophages are greatly influenced by the degree and nature of stimulation possibly affecting only a subpopulation of the cells. Accessory cell activity is also a function of a minor population of macrophages which have distinct surface antigens. The sources of the heterogeneity and the interrelationship between the macrophages subpopulations remain to be determined.

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“…McIntyre et al [85] found a wide variation in the bactericidal capacity of individual macro phages. In limited studies we have found that smaller macrophages, separated by sed imentation velocity, are somewhat more po tent than larger cells in killing Salmonella enteritidis in vitro [54].…”

Section: Activationmentioning

confidence: 99%

Macrophage Heterogeneity

Hopper¹,

Wood²,

Nelson³

1979

Vox Sanguinis

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Macrophages are a mobile, functionally diverse group of cells which may be recruited and stimulated to a high degree of metabolic activity. Heterogeneity may be detected from one site to another and result from local influences, e.g. lung v. peritoneal cells, or occur within a population and arise due to different stages of differentiation, maturation or activation or possibly from distinct cell lines. Recruitment and turnover are important determinants of the diversity of cells at any one site. In addition, anti-tumour, anti-microbial and secretory capacities of macrophages are greatly influenced by the degree and nature of stimulation possibly affecting only a subpopulation of the cells. Accessory cell activity is also a function of a minor population of macrophages which have distinct surface antigens. The sources of the heterogeneity and the interrelationship between the macrophage subpopulations remain to be determined.

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The Functional Heterogeneity of Macrophages at the Single Cell Level

Cited by 36 publications

References 8 publications

Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses

Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses

Macrophage Heterogeneity

Macrophage Heterogeneity

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