Related Experiment Video
Updated: Aug 9, 2026
Passive Administration of Monoclonal Antibodies Against H. capsulatum and Others Fungal Pathogens
Published on: February 15, 2011
CD4+ T cell-mediated fatal hyperinflammatory reactions in mice infected with Penicillium marneffei
N Kudeken1, K Kawakami, A Saito
1First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
Abstract:
In the present study, we demonstrate that all mice survived when a low dose of Penicillium marneffei was instilled intratracheally, while severe infection induced by instillation of 1 x 10(8) and 1 x 10(7) colony-forming units (CFU) killed all and 50% of mice, respectively, within 14 days, although the number of live microorganisms in the lungs of these animals was found to decrease with time. The cellular inflammatory responses in the lungs were much more striking in mice with severe infection than in animals infected with a low dose of microorganisms. The number of leucocytes, macrophages, neutrophils and lymphocytes in the lungs increased progressively during infection, and were more than 50 times higher on day 11 than in the control count. CD4+ T cells were the predominant cells in the lungs, and played an important role in hyperinflammatory host reactions, because neutralizing anti-CD4 MoAb increased the survival rate in infected mice despite the presence of a high number of live microorganisms in the lungs. Our results indicate that severe infection with P. marneffei induces fatal hyperinflammatory host reactions, mediated to a large extent by CD4+ T cells, although the infection is well controlled. However, the contribution of endogenous tumour necrosis factor-alpha (TNF-alpha) remains unsubstantiated, since administration of neutralizing anti-TNF-alpha MoAb in the present study failed to prolong survival in infected mice.
Insights
Severe Penicillium marneffei infection in mice triggers fatal hyperinflammatory responses, primarily driven by CD4+ T cells. Despite infection control, these reactions lead to mortality, highlighting a critical immune mechanism.
Area of Science:
- Immunology
- Infectious Diseases
- Microbiology
Background:
- Penicillium marneffei causes severe infections, particularly in immunocompromised individuals.
- Understanding host immune responses is crucial for managing P. marneffei infections.
Purpose of the Study:
- To investigate the host immune response to P. marneffei infection in mice.
- To determine the role of CD4+ T cells and tumor necrosis factor-alpha (TNF-alpha) in P. marneffei-induced hyperinflammation and mortality.
Main Methods:
- Mice were intratracheally instilled with varying doses of P. marneffei.
- Cellular inflammatory responses in the lungs were analyzed.
- The effect of neutralizing anti-CD4 monoclonal antibody (MoAb) and anti-TNF-alpha MoAb on survival was assessed.
Main Results:
- Severe P. marneffei infection led to significant mortality, correlated with striking cellular inflammatory responses in the lungs.
- CD4+ T cells were predominant and their depletion improved survival rates.
- Neutralizing anti-TNF-alpha MoAb did not prolong survival, suggesting TNF-alpha is not the primary mediator of hyperinflammation.
Conclusions:
- Severe P. marneffei infection induces fatal hyperinflammatory host reactions mediated by CD4+ T cells.
- While the infection itself is controlled, the host's inflammatory response contributes significantly to mortality.
- TNF-alpha does not appear to play a critical role in mediating these fatal reactions.
