Distinct innate immune responses between sublethal and lethal models of disseminated candidiasis in newborn BALB/c mice
Por:
Flores-Maldonado, Orlando E., Gonzalez, Gloria M., Andrade-Torres, Angel, Treviño-Rangel R., Donis-Maturano, Luis, Silva-Sanchez, Aaron, Hernandez-Bello, Romel, Montoya, Alexandra, Salazar-Riojas, Rosario, Romo-Gonzalez, Carolina, Becerril-Garcia, Miguel A.
Publicada:
1 sep 2021
Resumen:
Invasive candidiasis is associated with a high incidence and mortality
rates in infants, especially in preterm newborns. The immunopathogenesis
of the mycosis during the neonatal period is poorly understood. Although
several in vivo models exist to study invasive candidiasis, the majority
of studies employ distinct routes of infection and use 2 to 6 day-old
mice that could be less comparable in studying candidiasis in preterm
infants. In this study, by using 0-days-old mice we developed a new
neonatal murine model of intravenous Candida albicans infection. Using
different inoculums of Candida albicans we evaluated survival,
dissemination of the fungus, frequency of CD45(+) cells, and cytokine
production in the liver, brain, and kidneys of newborn and adult BALB/c
mice. Unexpectedly, the newborn mice infected with a low inoculum (1 x
10(5) cfu per mouse) of Candida albicans survive to the infection.
Compared to adult mice, the liver and brain of newborn animals had the
greatest fungal burden, fungal invasion and leukocyte infiltrate. A
moderate production of TNF alpha, IL-113, IL-6 and IFN gamma was
detected in tissues of newborn mice infected with a non-lethal inoculum
of Candida albicans. In contrast, overproduction of TNF alpha, IL-113,
IL-6 and IL-10 was determined when injecting with a lethal inoculum. In
agreement, flow cytometry of brain and liver showed an
inoculum-dependent CD45(+) leukocyte infiltration in newborn mice
infected with Candida albicans. Overall, our data shows that Candida
albicans infection in newborn mice affects mainly the brain and liver
and a 2-fold increase of the inoculum rapidly becomes lethal probably
due to massive fungal invasion and exacerbated CD45(+) leukocyte
infiltrate and cytokine production. This study is the first analysis of
innate immune responses in different tissues during early neonatal
disseminated candidiasis.
Filiaciones:
Flores-Maldonado, Orlando E.:
Departamento de Microbiología, Universidad Autónoma de Nuevo León, Facultad de Medicina y Hospital Universitario “Dr. José Eleuterio González”, Av. Francisco I. Madero, Mitras Centro, Monterrey, 64460, Mexico
Gonzalez, Gloria M.:
Departamento de Microbiología, Universidad Autónoma de Nuevo León, Facultad de Medicina y Hospital Universitario “Dr. José Eleuterio González”, Av. Francisco I. Madero, Mitras Centro, Monterrey, 64460, Mexico
Andrade-Torres, Angel:
Departamento de Microbiología, Universidad Autónoma de Nuevo León, Facultad de Medicina y Hospital Universitario “Dr. José Eleuterio González”, Av. Francisco I. Madero, Mitras Centro, Monterrey, 64460, Mexico
Becerril-Garcia, MA (Corresponding Author), Univ Autonoma Nuevo Leon, Dept Microbiol, Fac Med, Ave Francisco I Madero, Monterrey 64460, Mexico. Becerril-Garcia, MA (Corresponding Author), Hosp Univ Dr Jose Eleuterio Gonzalez, Ave Francisco I Madero, Monterrey 64460, Mexico. Flores-Maldonado, Orlando E
Treviño-Rangel R.:
Departamento de Microbiología, Universidad Autónoma de Nuevo León, Facultad de Medicina y Hospital Universitario “Dr. José Eleuterio González”, Av. Francisco I. Madero, Mitras Centro, Monterrey, 64460, Mexico
Donis-Maturano, Luis:
Unidad de Investigación en Biomedicina (UBIMED), Universidad Nacional Autónoma de México, Facultad de Estudios Superiores (FES)-IztacalaEstado de México, Mexico
Becerril-Garcia, MA (Corresponding Author), Univ Autonoma Nuevo Leon, Dept Microbiol, Fac Med, Ave Francisco I Madero, Monterrey 64460, Mexico. Becerril-Garcia, MA (Corresponding Author), Hosp Univ Dr Jose Eleuterio Gonzalez, Ave Francisco I Madero, Monterrey 64460, Mexico. Flores-Maldonado, Orlando E
Silva-Sanchez, Aaron:
Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
Becerril-Garcia, MA (Corresponding Author), Univ Autonoma Nuevo Leon, Dept Microbiol, Fac Med, Ave Francisco I Madero, Monterrey 64460, Mexico. Becerril-Garcia, MA (Corresponding Author), Hosp Univ Dr Jose Eleuterio Gonzalez, Ave Francisco I Madero, Monterrey 64460, Mexico. Flores-Maldonado, Orlando E
Hernandez-Bello, Romel:
Departamento de Microbiología, Universidad Autónoma de Nuevo León, Facultad de Medicina y Hospital Universitario “Dr. José Eleuterio González”, Av. Francisco I. Madero, Mitras Centro, Monterrey, 64460, Mexico
Becerril-Garcia, MA (Corresponding Author), Univ Autonoma Nuevo Leon, Dept Microbiol, Fac Med, Ave Francisco I Madero, Monterrey 64460, Mexico. Becerril-Garcia, MA (Corresponding Author), Hosp Univ Dr Jose Eleuterio Gonzalez, Ave Francisco I Madero, Monterrey 64460, Mexico. Flores-Maldonado, Orlando E
Montoya, Alexandra:
Departamento de Microbiología, Universidad Autónoma de Nuevo León, Facultad de Medicina y Hospital Universitario “Dr. José Eleuterio González”, Av. Francisco I. Madero, Mitras Centro, Monterrey, 64460, Mexico
Becerril-Garcia, MA (Corresponding Author), Univ Autonoma Nuevo Leon, Dept Microbiol, Fac Med, Ave Francisco I Madero, Monterrey 64460, Mexico. Becerril-Garcia, MA (Corresponding Author), Hosp Univ Dr Jose Eleuterio Gonzalez, Ave Francisco I Madero, Monterrey 64460, Mexico. Flores-Maldonado, Orlando E
Salazar-Riojas, Rosario:
Servicio de Hematología, Universidad Autónoma de Nuevo León, Facultad de Medicina y Hospital Universitario “Dr. José Eleuterio González”, Av. Francisco I. Madero, Mitras Centro, Monterrey, 64460, Mexico
Becerril-Garcia, MA (Corresponding Author), Univ Autonoma Nuevo Leon, Dept Microbiol, Fac Med, Ave Francisco I Madero, Monterrey 64460, Mexico. Becerril-Garcia, MA (Corresponding Author), Hosp Univ Dr Jose Eleuterio Gonzalez, Ave Francisco I Madero, Monterrey 64460, Mexico. Flores-Maldonado, Orlando E
Romo-Gonzalez, Carolina:
Laboratorio de Bacteriología Experimental, Instituto Nacional de Pediatría (INP)Ciudad de México, Mexico
Becerril-Garcia, MA (Corresponding Author), Univ Autonoma Nuevo Leon, Dept Microbiol, Fac Med, Ave Francisco I Madero, Monterrey 64460, Mexico. Becerril-Garcia, MA (Corresponding Author), Hosp Univ Dr Jose Eleuterio Gonzalez, Ave Francisco I Madero, Monterrey 64460, Mexico. Flores-Maldonado, Orlando E
Becerril-Garcia, Miguel A.:
Departamento de Microbiología, Universidad Autónoma de Nuevo León, Facultad de Medicina y Hospital Universitario “Dr. José Eleuterio González”, Av. Francisco I. Madero, Mitras Centro, Monterrey, 64460, Mexico
|