Effect of genetic modifications by selection for immunological tolerance on fungus infection in mice.
Two strains of mice genetically selected for extreme phenotypes of immunological tolerance to ovalbumin, susceptible (TS) and resistant (TR), were experimentally infected with Sporothrix schenckii. The objective was to observe whether the genetic modifications produced by the selection might be associated with interstrain differences in adaptive immune and innate responses to infection. Therefore, we evaluated the LD(50), CFU, phagocytic index, fungicidal activity, pro-inflammatory cytokines, specific antibody titres, and the delayed-type hypersensitivity reactivity. TR mice were tenfold more susceptible to infection than TS mice, as shown by LD(50) (5 x 10(6) conidia i.v.). In TS mice, the resistance was a consequence of the tissue fungal load reduction, consistent specific T-cell-mediated immunity, and tumour necrosis factor (TNF)-alpha activity at onset of infection. In TR mice, these responses were not precociously detected. Therefore, the absence of CD4(+) T-cell response in the first week of infection might explain the non-clearance of pathogen in TR mice. However, TR mice did show an increase in TNF level and delayed-type hypersensitivity response after the first week post-infection; there was also expansion and increase in granulomatous foci and CFU in the spleen. The expansion of granulomatous foci and the increase in TNF-alpha and tissue fungal load to damaging levels induced severe tissue destruction, general failure of the organs, cachexy and death in TR mice. The results show that genetic selection for extreme phenotypes of immunological tolerance also modified the responses to S. schenckii infection.
da Silva
A C
AC
Laboratório de Imunogenética, Departamento de Biologia Celular e Genética, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. dasilva@uerj.br
Bezerra
L M
LM
Aguiar
T S
TS
Tavares
D
D
Araujo
L M
LM
Pinto
C E
CE
Ribeiro
O G
OG
D000818:Animals; D020022:Genetic Predisposition to Disease; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics*; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000097:blood; D007928:Lethal Dose 50; D008264:Macrophages / Q000276:immunology; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D010587:Phagocytosis; D012641:Selection, Genetic; D013175:Sporothrix / Q000302:isolation & purification; D013174:Sporotrichosis / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D010047:Ovalbumin