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Published on: September 19, 2016
Pulmonary immune responses induced in BALB/c mice by Paracoccidioides brasiliensis conidia
Angel González1, Angela Restrepo, Luz Elena Cano
1Medical and Experimental Mycology Group, Corporación para Investigaciones Biológicas, CIB, Medellin, Colombia.
Abstract:
Knowledge concerning the host-Paracoccidioides brasiliensis interactions is abundant. Yet, most of the experimental studies have used yeast cells to prepare the corresponding inoculum. As these cells do not represent the naturally infecting propagules, the corresponding experiments by-pass the earlier stages of such interactions. Studies done in patients, who also harbour yeast cells, suffer from the same bias. The review presented below focuses on the immune responses of BALB/c mice infected with conidia obtained from P. brasiliensis mycelial form cultures, the fungal stage most probably existing in nature. As such, the corresponding experiments would copy the onset and course of the human infection. A large number of experimental studies done by the CIB Medical and Experimental Mycology Unit in a period of almost 25 years have been revised and extracted so as to present a comprehensive record on the immune responses induced when mice are infected intranasally with the conidia. The establishment of this mouse model has permitted the analysis of the immune responses taking place during the early and late stages post-challenge. This unique model has made possible to characterize the course of the experimental disease including the inflammatory reaction, the expression of cytokines and of the various molecules associated to these responses, all of which lead to granuloma formation. The latter structure serves as a nest for the development of fibrosis. Thus, we have also obtained a glimpse on the complexity that accompanies the fibrosis, the most common sequelae of paracoccidioidomycosis. Additionally, a concerted effort has been made to appraise the whole gamut of immune factors and related molecules that directly or indirectly, contribute to shape the pathogenesis of this Latin American mycosis.
Insights
This review details immune responses in BALB/c mice infected with Paracoccidioides brasiliensis conidia, mimicking human infection. It analyzes early and late-stage responses, inflammation, cytokines, and granuloma formation, offering insights into paracoccidioidomycosis pathogenesis.
Area of Science:
- Medical Mycology
- Immunology
- Infectious Diseases
Background:
- Most studies on host-Paracoccidioides brasiliensis interactions use yeast cells, which are not the naturally infecting propagules.
- This approach bypasses crucial early infection stages and introduces bias in understanding the disease.
- Human studies also often analyze yeast cells, limiting insights into the initial host response.
Purpose of the Study:
- To review experimental studies on immune responses in BALB/c mice infected with P. brasiliensis conidia.
- To establish a mouse model that accurately replicates the onset and progression of human paracoccidioidomycosis.
- To comprehensively analyze immune responses during early and late stages of infection.
Main Methods:
- Revision and extraction of experimental studies conducted over 25 years by the CIB Medical and Experimental Mycology Unit.
- Intranasal infection of BALB/c mice with P. brasiliensis conidia to mimic natural infection.
- Analysis of immune responses, including inflammatory reactions, cytokine expression, and molecule association.
Main Results:
- The established mouse model allows for the characterization of experimental paracoccidioidomycosis, including inflammatory processes.
- Detailed analysis of cytokine expression and associated molecules leading to granuloma formation.
- Insights into the development of fibrosis, a common sequela of paracoccidioidomycosis, and its associated complexities.
Conclusions:
- The conidia-infected mouse model provides a valuable tool for studying the pathogenesis of paracoccidioidomycosis.
- Understanding the immune response, granuloma formation, and fibrosis is crucial for managing this Latin American mycosis.
- Further research on immune factors and molecules is needed to fully elucidate the disease's progression.

