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Increased susceptibility to mouse hepatitis virus 3 of peritoneal macrophages exposed to dieldrin
Abstract:
Interaction of a single dose (36 mg/kg body wt) of the organochlorine pesticide dieldrin with mouse peritoneal macrophages was examined in C57Bl/6, (C57Bl/6 X A/J)F1, and A/J strains of different genetic resistance to mouse hepatitis virus 3 (MHV3) infection. In vivo studies showed increased susceptibility to MHV3 acute disease of C57Bl/6 and (C57Bl/6 X A/J)F1 animals challenged with the pesticide. Significant decrease of mean time of death in dieldrin-exposed, MHV3-infected susceptible C57Bl/6 mice was observed similarly upon po or ip administration of a single, sublethal dose of dieldrin. In addition, decrease of humoral response to the virus was quantified by determination of anti-MHV3 IgG antibodies in spleen cell supernatant fractions and in blood sera of dieldrin-exposed C57Bl/6 mice. A single dose of dieldrin did not alter the in vivo resistance of A/J animals to acute MHV3 disease. The resistant A/J mice, however, showed increased mortality upon two subsequent exposures to dieldrin followed by infection with high lethal doses of MHV3. Phagocytic activity, cell adherence capacity, and attachment and uptake of 3H-radiolabeled MHV3 by C57Bl/6 peritoneal macrophages were determined by in vitro studies. These affector activities of peritoneal macrophages were slightly decreased or unchanged in cells originating from animals exposed to the pesticide. However, the intrinsic activity of MHV3 restriction appeared to be affected in macrophages derived from dieldrin-treated animals: (i) peritoneal C57Bl/6 macrophages collected from the early phase of acute MHV3 disease contained increased MHV3 antigen and (ii) increased cytolysis was observed after in vitro MHV3 infection of macrophages originating from dieldrin-exposed C57Bl/6 mice.
Insights
The organochlorine pesticide dieldrin increases susceptibility to mouse hepatitis virus 3 (MHV3) infection in mice. Dieldrin exposure impairs macrophage antiviral activity, enhancing MHV3 disease severity and mortality.
Area of Science:
- Immunotoxicology
- Virology
- Environmental Health
Background:
- Organochlorine pesticides like dieldrin can impact immune function.
- Mouse hepatitis virus 3 (MHV3) is a significant pathogen in mice, with varying genetic resistance observed.
- Understanding the interplay between environmental toxins and viral infections is crucial for public health.
Purpose of the Study:
- To investigate the effects of dieldrin exposure on MHV3 infection susceptibility and severity in different mouse strains.
- To examine the impact of dieldrin on macrophage function and antiviral activity.
- To assess the influence of dieldrin on humoral immune responses to MHV3.
Main Methods:
- Mice of different genetic backgrounds (C57Bl/6, A/J, and F1 hybrids) were exposed to dieldrin and subsequently infected with MHV3.
- In vivo studies assessed mortality, mean time to death, and humoral immune response (anti-MHV3 IgG antibodies).
- In vitro studies evaluated peritoneal macrophage functions including phagocytosis, adherence, viral attachment/uptake, and MHV3 replication.
Main Results:
- Dieldrin exposure increased susceptibility and mortality to MHV3 in C57Bl/6 and F1 mice, significantly reducing survival time.
- Humoral immune response, measured by anti-MHV3 IgG, was decreased in dieldrin-exposed C57Bl/6 mice.
- While some macrophage effector functions were slightly altered, dieldrin-treated macrophages showed impaired intrinsic antiviral activity, with increased viral antigen and cytolysis post-infection.
Conclusions:
- Dieldrin exposure exacerbates MHV3 disease in susceptible mouse strains by compromising macrophage antiviral defense mechanisms.
- The findings highlight the immunotoxic potential of dieldrin and its role in increasing vulnerability to viral infections.
- Genetic resistance plays a role, but even resistant strains may show increased susceptibility with repeated dieldrin exposure and high viral doses.