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Genetic linkage of resistance to Listeria monocytogenes with macrophage inflammatory responses
Abstract:
The mobilization of adequate numbers of mononuclear phagocytes to inflammatory foci was measured in Listeria-resistant and Listeria-sensitive mice. Resistant strains, such as B10.A, were found to have a 2- to 3-fold greater accumulation of peritoneal macrophages after i.p. treatment with a variety of nonspecific inflammatory stimuli in comparison to sensitive strains, such s A/J. In addition to low macrophage inflammatory responses, A/J mice had fewer resident peritoneal macrophages. Moreover, measurement of chemotaxis in vitro of equal numbers of thioglycollate-induced macrophages showed cells from A/J mice to be less responsive to complement-derived chemotactic factors. Thus, the mononuclear phagocyte systems of resistant B10.A and sensitive A/J mice were quantitatively and qualitatively different. A survey of inbred mouse strains revealed that these differences were not peculiar to A strain mice and that, in general, the level of the in vivo macrophage inflammatory response correlated with the level of resistance to Listeria in a given strain. Like resistance to Listeria, the macrophage inflammatory response was found to be genetically controlled by an autosomal, non-H-2-linked gene(s) expressed as incompletely dominant. Backcross analysis showed genetic linkage of the macrophage inflammatory response with resistance to Listeria. Thus, the results of this study provide formal evidence that the cellular basis of the genetically determined, enhanced resistance to Listeria is an augmented pool size of mononuclear phagocytes, and the prompt mobilization of these cells to foci of infection.
Insights
Listeria-resistant mice exhibit a greater accumulation of mononuclear phagocytes at inflammatory sites compared to sensitive strains. This enhanced macrophage response, controlled by specific genes, is key to genetically determined resistance to Listeria infection.
Area of Science:
- Immunology
- Genetics
- Microbiology
Background:
- The immune system's ability to recruit mononuclear phagocytes is crucial for combating infections.
- Differences in immune responses between mouse strains can influence susceptibility to pathogens like Listeria.
Purpose of the Study:
- To investigate the quantitative and qualitative differences in mononuclear phagocyte mobilization between Listeria-resistant and Listeria-sensitive mice.
- To determine the genetic basis and linkage of macrophage inflammatory responses with Listeria resistance.
Main Methods:
- Comparing peritoneal macrophage accumulation in vivo following inflammatory stimuli in resistant (B10.A) and sensitive (A/J) mouse strains.
- Assessing macrophage chemotaxis in vitro using complement-derived factors.
- Analyzing the genetic control and linkage of macrophage inflammatory response and Listeria resistance through backcross analysis.
Main Results:
- Listeria-resistant mice showed a 2- to 3-fold greater accumulation of peritoneal macrophages compared to sensitive mice.
- Sensitive mice (A/J) exhibited lower macrophage inflammatory responses and fewer resident peritoneal macrophages.
- Macrophages from sensitive mice were less responsive to chemotactic factors in vitro.
- Macrophage inflammatory response and Listeria resistance are genetically controlled by autosomal, non-H-2-linked genes and are genetically linked.
Conclusions:
- The cellular basis for genetically determined enhanced resistance to Listeria is an augmented pool size and prompt mobilization of mononuclear phagocytes.
- Quantitative and qualitative differences in the mononuclear phagocyte system contribute to varying levels of Listeria resistance among mouse strains.