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Spacious phagosome formation within mouse macrophages correlates with Salmonella serotype pathogenicity and host
C M Alpuche-Aranda1, E P Berthiaume, B Mock
1Infectious Diseases Unit, Massachusetts General Hospital, Boston 02114, USA.
Abstract:
Light microscopic studies indicated a correlation between the virulence for mice of different Salmonella serotypes and the ability to form or maintain spacious phagosomes (SP) within mouse macrophages. Although Salmonella typhimurium induced membrane ruffling, macropinocytosis, and SP formation in macrophages from BALB/c mice, serotypes which are nonpathogenic for mice produced markedly fewer SP. SP formation correlated with both serotype survival within mouse macrophages and reported lethality for mice. Time-lapse video microscopy demonstrated that the human pathogen S. typhi induced generalized macropinocytosis and SP formation in human monocyte-derived macrophages, indicating a similar morphology for the initial phases of this host-pathogen interaction. In contrast to bone marrow-derived macrophages from BALB/c mice, macrophages from S. typhimurium-resistant outbred (CD-1) and inbred (CBA/HN) mice did not initiate generalized macropinocytosis after bacterial infection and formed markedly fewer SP. These deficiencies were not due to the Ihy resistance genotype of these mice, as macrophages from mice that were congenic except for the Ihy locus demonstrated equal SP formation in response to S. typhimurium. The observation that S. typhimurium-resistant CD-1 and CBA/HN mice are deficient in the ability to form and/or maintain SP indicates that a variable host component is important for SP formation and suggests that the ability to induce or form SP affects susceptibility to S. typhimurium. When serotypes nonpathogenic for mice were used to infect BALB/c macrophages, or when CD-1 or CBA/HN mouse macrophages were infected by S. typhimurium, some of the SP that formed shrank within seconds. This rapid shrinkage suggests that SP maintenance is also important for S. typhimurium survival within macrophages. These studies indicate that both host and bacterial factors contribute to SP formation and maintenance, which correlate with Salmonella intracellular survival and the ability to cause lethal enteric (typhoid) fever.
Insights
Salmonella virulence correlates with spacious phagosome (SP) formation in macrophages. Host factors influence SP formation and maintenance, impacting bacterial survival and disease severity.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Salmonella serotypes exhibit varying virulence in mice.
- The intracellular survival of Salmonella within host macrophages is a key factor in pathogenesis.
- Spacious phagosomes (SP) are cellular compartments within macrophages that can harbor bacteria.
Purpose of the Study:
- To investigate the correlation between Salmonella virulence and the ability to form spacious phagosomes (SP) in macrophages.
- To explore host factors influencing SP formation and maintenance.
- To understand the role of SP in Salmonella intracellular survival and host susceptibility.
Main Methods:
- Light microscopy to observe SP formation in infected macrophages.
- Time-lapse video microscopy to analyze host-pathogen interactions.
- Infection of macrophages from different mouse strains with various Salmonella serotypes.
Main Results:
- Salmonella typhimurium induced SP formation in BALB/c mouse macrophages, while nonpathogenic serotypes induced fewer SP.
- SP formation correlated with Salmonella serotype virulence and lethality in mice.
- Macrophages from S. typhimurium-resistant mice showed reduced SP formation, indicating a host-dependent component.
- Rapid shrinkage of SP was observed, suggesting that SP maintenance is crucial for bacterial survival.
Conclusions:
- Both host and bacterial factors contribute to SP formation and maintenance.
- The ability to induce or form SP is linked to Salmonella intracellular survival and host susceptibility.
- SP dynamics play a significant role in the pathogenesis of Salmonella infections, including typhoid fever.