Impact of prophylactic ganciclovir on bronchoalveolar lavage lymphocyte numbers and phenotypes in murine cytomegalovirus-induced reactivation of Toxoplasma pneumonia.
In a mouse model of cytomegalovirus (CMV)-induced immunosuppression, murine CMV (MCMV) infection results in reactivation of Toxoplasma pneumonia, and prophylactic but not delayed administration of ganciclovir attenuates the severity of this pneumonia. We now report that the protection observed with ganciclovir is associated with blunting of the alterations in bronchoalveolar lavage (BAL) lymphocyte numbers and phenotypes observed in untreated mice. Specifically, prophylactic ganciclovir prevents the usual drop in BAL CD4+ lymphocytes observed in the first week after MCMV injection--that is, the period of MCMV-associated immunosuppression. Furthermore, prophylactic ganciclovir markedly blunts the usual rise in BAL T lymphocytes (CD8+ > CD4+) seen later during the peak of reactivated Toxoplasma pneumonia. These findings suggest that prophylactic ganciclovir can protect animals from virus-associated opportunistic pneumonia by attenuating virus-induced changes in BAL lymphocytes and the attendant suppression of lung immunity.
Goetz
L
L
Division of Infectious Diseases, Department of Medicine, University of Kentucky Medical School, USA.
Pomeroy
C
C
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015774:Ganciclovir / Q000494:pharmacology*; D016130:Immunophenotyping; D018655:Lymphocyte Count / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000276:immunology; D011014:Pneumonia / Q000469:parasitology* / Q000517:prevention & control / Q000821:virology; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors; D014122:Toxoplasma / Q000276:immunology / Q000821:virology; D014124:Toxoplasmosis, Animal / Q000188:drug therapy / Q000276:immunology* / Q000821:virology
D000998:Antiviral Agents; D015774:Ganciclovir