Therapeutic effect of monophosphoryl lipid A administration onParacoccidioides brasiliensis–infected mice

Abstract

The lack of antifungals with low toxicity and short-term therapy for patients with paracoccidioidomycosis (PCM) led us to evaluate adjuvants in immunotherapeutic intervention. We have previously shown complete Freund's adjuvant (CFA) to be therapeutic on experimental PCM. Owing to CFA toxicity, here we tested adjuvants approved for clinical use or in preclinical phase in experimental mouse PCM. Of all, only monophosporyl lipid A (MPLA) demonstrates a beneficial effect, by reducing the fungal burden and increasing the concentrations of IFN-γ and TNF-α, which are immunoprotective in PCM. These results suggest that MPLA might improve intervention in PCM.

Quantitation of pulmonary fungal burden in Paracoccidioides brasiliensis-infected mice by real-time PCR

“…Therefore, the protocol here developed proved to be efficient and enabled the evaluation of treatment performed in P. brasiliensis-infected mice. In this trial, it was clear that MPLA significantly decreased the fungal load, as previously described 14 . Taking into consideration that these small variations were identified only among the analyzed methods, but maintained the same results found between PBS and MPLA groups, the quantification method of pulmonary fungal burden by real-time PCR is a potential tool for investigations in experimental PCM in mice.…”

“…None of them became seriously ill or died prior to the experimental endpoint. The treatment protocol was carried out as previously described 14 . Briefly, groups of five infected mice were subcutaneously injected on day 21 after infection with 100 μL of monophosphoryl lipid A from Salmonella minnesota (MPLA, Invivogen, San Diego, USA) and phosphate buffered saline (PBS).…”

Boosting Toll-like receptor 4 signaling enhances the therapeutic outcome of antibiotic therapy in pneumococcal pneumonia

“…These observations demonstrated that MPLA could potentially function as a therapeutic agent. On the same lines, a recent study evidenced the therapeutic effect of MPLA-containing adjuvants in the context of systemic mycosis (19). Another study reported that administration of LPS, the highly pyrogenic and toxic TLR4 agonist with antibiotic is able to eliminate Salmonella invading the mesenteric lymph nodes, in contrast to stand-alone antibiotic treatment (23).…”

“…In view of these observations, we hypothesized that MPLA may be a viable treatment against an ongoing bacterial infection, and so looked into both its applicability and efficacy as an anti-infective therapy. To the best of our knowledge, the only other previous study of this approach was performed in the context of fungal infection (19).…”