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Updated: Jun 25, 2026
Isolation of Mouse Lung Dendritic Cells
Published on: November 22, 2011
Cryptococcal urease promotes the accumulation of immature dendritic cells and a non-protective T2 immune response
John J Osterholzer1, Rishi Surana, Jami E Milam
1Veterans Affairs Ann Arbor Health System, Ann Arbor, 2215 Fuller Rd., Ann Arbor, MI 48105, USA. olszewsm@umich.edu
Abstract:
Urease, a major virulence factor for Cryptococcus neoformans, promotes lethal meningitis/encephalitis in mice. The effect of urease within the lung, the primary site of most invasive fungal infections, is unknown. An established model of murine infection that utilizes either urease-producing (wt and ure1::URE1) or urease-deficient (ure1) strains (H99) of C. neoformans was used to characterize fungal clearance and the resultant immune response evoked by these strains within the lung. Results indicate that mice infected with urease-producing strains of C. neoformans demonstrate a 100-fold increase in fungal burden beginning 2 weeks post-infection (as compared with mice infected with urease-deficient organisms). Infection with urease-producing C. neoformans was associated with a highly polarized T2 immune response as evidenced by increases in the following: 1) pulmonary eosinophils, 2) serum IgE levels, 3) T2 cytokines (interleukin-4, -13, and -4 to interferon-gamma ratio), and 4) alternatively activated macrophages. Furthermore, the percentage and total numbers of immature dendritic cells within the lung-associated lymph nodes was markedly increased in mice infected with urease-producing C. neoformans. Collectively, these data define cryptococcal urease as a pulmonary virulence factor that promotes immature dendritic cell accumulation and a potent, yet non-protective, T2 immune response. These findings provide new insights into mechanisms by which microbial factors contribute to the immunopathology associated with invasive fungal disease.
Insights
Cryptococcus neoformans urease increases fungal burden in the lungs, promoting a strong but non-protective T2 immune response and immature dendritic cell accumulation. This highlights urease as a pulmonary virulence factor.
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- Urease is a key virulence factor for Cryptococcus neoformans, often causing lethal meningitis.
- The role of urease in the lung, the primary site of fungal infection, remains unclear.
- Cryptococcus neoformans is a significant human pathogen, particularly in immunocompromised individuals.
Purpose of the Study:
- To investigate the impact of Cryptococcus neoformans urease on fungal clearance and immune response within the murine lung.
- To determine if urease contributes to virulence in the pulmonary environment.
- To characterize the specific immune pathways modulated by urease during pulmonary cryptococcosis.
Main Methods:
- Utilized a murine infection model with urease-producing and urease-deficient Cryptococcus neoformans strains (H99).
- Quantified fungal burden in the lungs at various time points post-infection.
- Analyzed immune cell populations (eosinophils, macrophages, dendritic cells) and cytokine profiles (T2 cytokines, IgE) in lung tissue and associated lymph nodes.
Main Results:
- Mice infected with urease-producing strains showed a 100-fold increase in fungal burden compared to those with urease-deficient strains.
- Pulmonary infection with urease-producing C. neoformans induced a highly polarized T2 immune response, marked by increased eosinophils, serum IgE, and T2 cytokines (IL-4, IL-13).
- Increased numbers of alternatively activated macrophages and immature dendritic cells were observed in the lungs and lung-associated lymph nodes, respectively.
Conclusions:
- Cryptococcal urease acts as a pulmonary virulence factor, significantly increasing fungal burden.
- Urease promotes the accumulation of immature dendritic cells and drives a potent but non-protective T2 immune response in the lung.
- These findings offer novel insights into how microbial factors contribute to the immunopathology of invasive fungal infections.
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