The threat posed to hospitalized patients due to fungal infection is attributable to: (i) Lack of a sensitive, rapid and accurate diagnostic assays for invasive fungal infection, (ii) antifungal drugs have only modest success in reducing the high mortality rates of invasive mycoses and are inactive against newly emerging antifungal-resistant strains; the cost of treating Aspergillus (the most common human fungal pathogens) infections in Europe is approximately €80,000 per patient and the annual cost of administering antifungal agents often overrides that of antibacterial agents, (iii) The pathobiology of fungal infections remains poorly understood and (iv) The population of patients at risk is steadily increasing. Even in India, Aspergillus is becoming medically important as they cause most prevalent invasive fungal infections. Accordingly, this project proposal is centered on Aspergillus fumigatus, though a saprophyte growing on decaying vegetation is the most ubiquitous opportunistic human fungal pathogen world-wide. It causes a number of diseases such as lung/sinus aspergilloma and allergic bronchopulmonary aspergillosis in the predisposed immunocompetent human population. However, the most fatal one is the invasive aspergillosis (IA), a systemic infection in the immunocompromised individuals; the frequency of IA has risen more than 10-folds worldwide in the last two decades. A. fumigatus conidia entering the human lung alveoli are confronted with the innate immune system, both cellular barriers and soluble mediators. The role played by the cellular barriers in evading A. fumigatus is quite well studied but that of the soluble mediators (the complement system, collectins and antimicrobial peptides) is mostly ignored. The cellular barriers are mainly resident alveolar macrophages, polymorphonuclear neutrophils (PMNs) and respiratory epithelial cells. The soluble mediators are playing a central role as innate immune effector elements against invading microbes; but their mechanisms of action against A. fumigatus are unknown. On the other hand, A. fumigatus exploit several strategies to evade host defense: in the conidial stage, the surface rodlet layer masks their immune recognition and during vegetative growth proteins secreted are reported to evade host defense thus contributing for the pathogenicity. Our proposed project is focussed on the interaction between A. fumigatus and the soluble mediators of the innate immune system. Accordingly, the main goals are: Host - fungus: To understand the exact role played by the soluble mediators as immune effector elements against A. fumigatus. Fungus - host: To understand the role of A. fumigatus secreted proteins (secretome) in establishing pathogenicity by acting against defense mechanisms played by the soluble mediators of the immune system. Our objectives are innovative and of medical importance, combining the three themes of Blanc SVSE3 microbiology-immunology-infection program. Interest in this International collaboration is that, combating invasive fungal infection is the aim of both the countries participating in the proposed project and the partners complement one another in achieving proposed goals. A face-to-face discussion was made among the partners during the Franco-Indian Symposium (HOPE IN RED) sponsored by CEFIPRA [Bangalore, India, 2010] to initiate this collaboration. We (Partner n°1) have experience in the field of fungal biology. Dr. Taruna Madan’s (Partner n°3; India) theme of work is the role of collectins in the A. fumigatus infection, while Dr. Arvind Sahu (Partner n°2; India) has got expertise in the complement system field (particularly, viral complement invasion) and enthusiastic to enter the fungal-field. Due to the development of resistance, search for the new antifungal drugs is of global thrust and outcome of our proposed project might bring out future collaborations in developing new such antifungal drugs.