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Resolution of invasive fungal infections is often dependent on recovery from an immunocompromised state, indicating that host defense mechanisms are extremely important in the clearance of fungal pathogens. Immunotherapy aimed at enhancing host defense mechanisms may improve clinical outcome of invasive mycoses. Recombinant cytokines and growth factors have been applied in vitro and in animal models to augment host defense mechanisms that are involved in invasive fungal infections. In patients with invasive mycoses, prospective phase 2 studies with recombinant G-CSF and IFNγ have been performed. Recombinant IFNγ is a candidate for phase 3 trials on adjunctive immunotherapy for cryptococcal meningitis, invasive aspergillosis and candidemia [ABSTRACT FROM AUTHOR]

Toll-like receptors (TLRs) have been identified as a major class of pattern-recognition receptors. Recognition of pathogen-associated molecular patterns (PAMPs) by TLRs, either alone or in heterodimerization with other TLR or non-TLR receptors, induces signals responsible for the activation of innate immune response. Recent studies have demonstrated a crucial involvement of TLRs in the recognition of fungal pathogens such as Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans. By studying fungal infections in knock-out mice deficient in either TLRs or TLR-associated adaptor molecules, it appeared that specific TLRs such as TLR2, TLR4, TLR6 and TLR9 play differential roles in the activation of the various arms of the innate immune response. In addition, stimulation of TLR2 can also induce immunological tolerance and in certain conditions offer escape mechanisms, especially through induction of antiinflamatory cytokines. These developments provide crucial information for understanding the mechanisms of fungal recognition by cells of the immune system, and provide hope for designing new therapeutical approaches to fungal infections [ABSTRACT FROM AUTHOR]

In the course of evolution nature has provided the normal human individual with an impressive and effective defense system against microbial enemies that eclipses even Star Wars, arguably the most advanced and ingenious defense program ever designed by human beings. On its own, the normal defense system recognizes foreign invaders, alerts the relevant protective mechanisms, launches counterattacks, ceases hostilities as soon as the job is done, and clears up the battlefield, causing only negligible collateral damage. An intact system offers protection against most microbial aggressors through a complex interrelationship of protecting surfaces, cells, and soluble factors. [ABSTRACT FROM AUTHOR]