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Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

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Mannose-binding lectin complement pathway plays a key role in complement activation by Paracoccidioides brasiliensis.

Renan G Toledo¹, Wilmar D Da Silva, Vera L G Calich

¹Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense, Darcy Ribeiro. Av. Alberto Lamego, 2000, Parque Califórnia, Campos dos Goytacazes, RJ, CEP: 28013-602, Brazil.

Molecular Immunology

|November 2, 2010

Summary

Paracoccidioides brasiliensis (Pb) activates the complement system via the lectin pathway. Lower virulence fungal strains exhibit stronger complement activation, suggesting an inverse correlation with disease severity.

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Area of Science:

* Mycology
* Immunology
* Infectious Diseases

Background:

* Paracoccidioides brasiliensis (Pb) causes paracoccidioidomycosis, a severe South American deep mycosis.
* Cell-mediated immunity is key, but innate immune mechanisms against Pb are not well understood.
* The complement system's role in Pb infection requires further investigation.

Purpose of the Study:

* To investigate the interaction between complement system components and high/low virulence Pb isolates.
* To elucidate the complement activation pathway utilized by Pb.
* To determine the correlation between Pb virulence and complement activation.

Main Methods:

* Incubation of Pb isolates (high virulence Pb18, low virulence Pb265) with normal human serum (NHS) and MBL-sufficient/deficient sera.
* Assessed complement consumption (C4, C3) and deposition (C4b, C3b, C5b-C9, MBL) on fungal cells and immune complexes.
* Compared complement activation between wild-type and virulence-attenuated/reactivated Pb strains.

Main Results:

* Both Pb isolates consumed C4, C3, and MBL from MBL-sufficient serum, indicating lectin pathway activation.
* Low virulence Pb265 consumed more complement components than high virulence Pb18.
* Virulence attenuation of Pb18 increased complement activation; reactivation decreased it.

Conclusions:

* Pb yeasts activate the complement system primarily through the lectin pathway.
* There is an inverse correlation between Pb complement-activating ability and fungal virulence.
* These findings offer insights into innate immunity and paracoccidioidomycosis pathogenesis.