Anti- Aspergillus fumigatus Efficacy of Pentraxin 3 Alone and in Combination with Antifungals

Abstract

The collectin pentraxin 3 (PTX3) is an essential component of host resistance to pulmonary aspergillosis. Here we examined the protective effects of administration of PTX3 alone or together with deoxycholate amphotericin B (Fungizone) or liposomal amphotericin B (AmBisome) against invasive aspergillosis in a murine model of allogeneic bone marrow transplantation. PTX3, alone or in combination with the polyenes, was given intranasally or parenterally either before, in concomitance with, or after the intranasal infection with Aspergillus fumigatus conidia. Mice were monitored for resistance to infection and parameters of innate and adaptive T-helper immunity. The results showed the following: (i) complete resistance to infection and reinfection was observed in mice treated with PTX3 alone; (ii) the protective effect of PTX3 was similar or superior to that observed with liposomal amphotericin B or deoxycholate amphotericin B, respectively; (iii) protection was associated with accelerated recovery of lung phagocytic cells and T-helper-1 lymphocytes and concomitant decrease of inflammatory pathology; and (iv) PTX3 potentiated the therapeutic efficacy of suboptimal doses of either antimycotic drug. Together, these data suggest the potential therapeutic use of PTX3 either alone or as an adjunctive therapy in A. fumigatus infections.

Structural Characterization of PTX3 Disulfide Bond Network and Its Multimeric Status in Cumulus Matrix Organization

“…The observed fragmentation patterns were consistent with the sequence of peptide 315-332. Moreover identical mass values were measured for y 7 and y 8 fragments in both spectra. Because y 7 and y 8 ions both retained the peptide C-terminal end lacking cysteines 317 and 318, their observed molecular masses were 1--------*--------20---------*--------40---------*--------60---------*--------80---------*-------100 mhllailfcalwsavlaENSDDYDLMYVNLDNEIDNGLHPTEDPTPCDCGQEHSEWDKLFIMLENSQMRERMLLQATDDVLRGELQRLREELGRLAESLA 101------*-------120---------*-------140---------*-------160---------*-------180---------*-------200 RPCAPGAPAEARLTSALDELLQATRDAGRRLARMEGAEAQRPEEAGRALAAVLEELRQTRADLHAVQGWAARSWLPAGcetailfpmrskkifgsvhpvr 201------*-------220---------*-------240---------*-------260---------*-------280---------*-------300 pmrlesfsaciwvkatdvlnktilfsygtkrnpyeiqlylsyqsivfvvggeenklvaeamvslgrwthlcgtwnseegltslwvngelaattvematgh not affected by DTT treatment.…”

“…Studies performed on Ptx3-null (Ptx3 Ϫ/Ϫ ) mice have shown that this molecule has a number of functions in vivo. PTX3 acts as a soluble pattern recognition receptor with a nonredundant protective role against selected pathogens, mainly the opportunistic fungus Aspergillus fumigatus (6,7). PTX3 is also essential for correct assembly of the viscoelastic hyaluronan (HA) 4 -rich matrix surrounding the oocyte in the preovulatory follicle (namely, the cumulus oophorus).…”

Antiviral Activity of the Long Chain Pentraxin PTX3 against Influenza Viruses

“…16). Despite a well documented role in innate host defense against certain bacteria and fungi (17)(18)(19)(20), few studies have addressed the antiviral activities of PTX3. To this end, a recent study described the ability of human PTX3 to bind and inhibit the infectivity of human and murine cytomegaloviruses (21).…”

A sniff to chase ill humors away

“…7 In a murine HCT model, administration of PTX3 provided protection against the development of IA after an intranasal challenge. 8 These observations remind us that, although the flotilla of hematopoietic cells and circulating molecules that we normally think of providing protection are very important and often determinant in controlling infection, those are not the only host components of innate immunity. The anatomic barriers of skin, mucosa, and lung epithelia make up the first line of defense.…”