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Ontogeny of macrophage resistance to mouse hepatitis in vivo and in vitro
Abstract:
Adult or weanling C(3)H mice were found to be genetically resistant to a strain of mouse hepatitis virus. Infant C(3)H mice, however, developed infection and died from mouse hepatitis virus when minimal infectious doses of virus were given to them. There was a delay in the time of death compared to that of the genetically susceptible strain, and the virus recovered from these mice had increased pathogenicity for C(3)H mice. The ontogeny of resistance to hepatitis in the C(3)H mice thus progresses from delayed susceptibility to complete resistance as the age of the host increases. It is reflected in increased resistance of macrophages derived in vitro from liver cultures of infant mice of different ages. This increase in resistance with age was reduced by maintaining the cultures for a longer period of time before inoculation, or by increasing the number of explants in a given culture. Resistant cells were uniformly furnished by mice age 16 days, or more. It is concluded that a process of maturation of resistance of the cells takes place after the mice are born, but that this does not continue under in vitro conditions, and that it may be modified by the environment of the cells.
Insights
Young C(3)H mice are susceptible to mouse hepatitis virus (MHV), developing delayed infections. Resistance to MHV increases with age, indicating a maturation process in host defense mechanisms.
Area of Science:
- Virology
- Immunology
- Developmental Biology
Background:
- C(3)H mice exhibit genetic resistance to certain mouse hepatitis virus (MHV) strains.
- Infant C(3)H mice, however, are susceptible to MHV, succumbing to infection even with minimal viral doses.
Purpose of the Study:
- To investigate the ontogeny of resistance to mouse hepatitis virus in C(3)H mice.
- To understand the age-dependent development of resistance and its cellular basis.
Main Methods:
- Infection of infant and adult C(3)H mice with MHV.
- Isolation and characterization of MHV from infected mice.
- In vitro culture of macrophages from mice of different ages.
- Assessment of macrophage resistance to MHV infection.
Main Results:
- Infant C(3)H mice showed delayed mortality compared to susceptible strains, with recovered virus exhibiting increased pathogenicity.
- Macrophage resistance to MHV increased with the age of the mice from which they were derived.
- In vitro culture conditions, such as duration and cell density, influenced the observed resistance.
Conclusions:
- C(3)H mice develop resistance to MHV postnatally, a process of cellular maturation.
- This maturation of resistance is not sustained under prolonged in vitro culture conditions.
- The cellular environment plays a role in modulating the development of MHV resistance.