Role of IL-10 in invasive aspergillosis: increased resistance of IL-10 gene knockout mice to lethal systemic aspergillosis

Abstract

SUMMARYIL-10 is associated with a Th2 response, down-regulation of a Th1 response and macrophage activation. We assessed the role of IL-10 during systemic infection with Aspergillus fumigatus. Systemic aspergillosis was established in female C56Bl/6 IL-10 2/± (KO) and wild-type (WT) C57Bl/6 mice by i.v. administration of 1 Â 10 5 26 Â 10 5 conidia of A. fumigatus. In two experiments, KO survived longer than did WT (P , 0´001). Determination of fungal burdens in the kidneys and brain showed that KO carried significantly lower burdens in both organs than did WT on day 3 (P , 0´001). Semiquantitative histological analyses showed fewer inflammatory foci/mm 2 in brain and kidneys of KO than WT (P , 0´03 and , 0´001, respectively) and that extent of infection and associated tissue injury were greater in WT. Although beneficial in some bacterial infections, exogenous IL-10 has been shown deleterious in models of fungal infection. Our data indicate IL-10 is deleterious during systemic aspergillosis infection, increasing the host susceptibility to lethal infection. We speculate this might be related to greater Th2 or lesser Th1 responses, or down-regulation of macrophage responses, in WT compared with KO.

Innate Immunity toAspergillusSpecies

“…Immunocompetent IL-10-deficient animals were similarly resistant to infection when given intravenous conidia (43). Consistent with this, the presence of a human IL-10 promoter polymorphism resulting in reduced IL-10 expression levels in recipients of allogeneic bone marrow transplantation was associated with a reduced incidence of invasive aspergillosis (147,153).…”

Protective role of interleukin-10 promoter gene polymorphism in the pathogenesis of invasive pulmonary aspergillosis after allogeneic stem cell transplantation

“…For example, IL-10 pretreated human macrophages have been found to suppress superoxide production and decrease hyphal damage, thus increasing the risk of IPA, 22 while IL-10 deficient mice exhibit an upregulated antifungal response and increased resistance to lethal systemic aspergillosis. 23,24 Furthermore, in cortisonepretreated mice, A. fumigatus has been found to cause Years from transplantation IL-10 SNP in IPA after alloSCT KW Seo et al lethal invasive aspergillosis with high expression levels of IL-10 in the lungs. 25 Therefore, these results indicate that IL-10 plays a negative role as regards invasive aspergillosis in mice models.…”

CC Chemokine Receptor 7 Expression by Effector/Memory CD4+T Cells Depends on Antigen Specificity and Tissue Localization during Influenza A Virus Infection

“…It is known that IL-10 can be immunosuppressive in a number of infections by hampering the clearance of intracellular pathogens (12,17,26,41). On the other hand, the down-modulation of immune responses by IL-10 during infections protects the body from overwhelming destructive inflammatory responses (12,19,41). Therefore, the low migratory potential toward CCL21 of IL-10 producers in the lung during influenza may be a mechanism to retain the cells in the lung to prevent severe destruction of the organ during the inflammatory process.…”