The impact of ISGylation during Mycobacterium tuberculosis infection in mice.
Microbes Infect
; 19(4-5): 249-258, 2017.
Article
em En
| MEDLINE
| ID: mdl-28087453
ABSTRACT
Mycobacterium tuberculosis infection results in 1.5 million deaths annually. Type I interferon (IFN) signaling through its receptor IFNAR correlates with increased severity of disease, although how this increases susceptibility to M. tuberculosis remains uncertain. ISG15 is one of the most highly induced interferon stimulated genes (ISGs) during M. tuberculosis infection. ISG15 functions by conjugation to target proteins (ISGylation), by noncovalent association with intracellular proteins, and by release from the cell. Recent studies indicated that ISG15 can function via conjugation-independent mechanisms to suppress the type I IFN response. These data raised the question of whether ISG15 may have diverse and sometimes opposing functions during M. tuberculosis infection. To address this, we analyzed ISGylation during M. tuberculosis infection and show that ISGylated proteins accumulate following infection in an IFNAR-dependent manner. Type I IFN and ISG15 both play transient roles in promoting bacterial replication. However, as the disease progresses, ISGylation deviates from the overall effect of type I IFN and, ultimately, mice deficient in ISGylation are significantly more susceptible than IFNAR mice. Our data demonstrate that ISGs can both protect against and promote disease and are the first to report a role for ISGylation during M. tuberculosis infection.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tuberculose Pulmonar
/
Interferon Tipo I
/
Citocinas
/
Receptor de Interferon alfa e beta
/
Mycobacterium tuberculosis
Limite:
Animals
Idioma:
En
Revista:
Microbes Infect
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
MICROBIOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos