Lipopolysaccharide restores anti-Candida albicans growth inhibition activity of polymorphonuclear neutrophils from retrovirus-immunosuppressed mice

Abstract

It has been documented that the immune function of leukocytes may be markedly suppressed after infection of mice with the murine retrovirus Friend leukemia virus (FLV). Antimicrobial activity of polymorphonuclear neutrophils (PMNs) against Candida albicans is impaired after retrovirus infection of mice, and this occurs as early as 3 days after infection of genetically susceptible BALB/c mice. By 2 weeks after infection, there was essentially very little growth inhibition of C. albicans by PMNs from the FLV-infected mice. However, when bacterial lipopolysaccharide (LPS), a known activator of macrophages and PMNs, was added to PMNs from the FLV-infected mice, anti-C. albicans activity was restored to normal levels. This restoration of anti-C. albicans activity of FLV-infected mouse PMNs was observed after stimulation with as little as 0.01 ,ug of LPS per ml. The data obtained show that the impaired antimicrobial function of PMNs from retrovirus-infected mice can be readily restored by a biological response modifier such as bacterial LPS.

TLR Signaling Rescues Fungicidal Activity in Syk-Deficient Neutrophils

“…Given TLR expression on neutrophils, we examined TLR agonists as potential alternative activation signaling pathways. Previous data support the augmentation of neutrophil fungicidal activity through TLR4 recognition of LPS (38). Interestingly, TLR4 also has the capacity to recognize C. albicans through the recognition of cell wall O-mannan (39) and to trigger downstream Syk activation, further complicating potential mechanisms of Syk-independent activation through TLRs (40).…”