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Elimination of mouse splenic macrophages correlates with increased susceptibility to experimental disseminated
Q Qian1, M A Jutila, N Van Rooijen
1Department of Microbiology, Montana State University, Bozeman, MT 59717.
Abstract:
To evaluate the role of macrophages in experimental disseminated candidiasis, mouse splenic macrophages were eliminated by i.v. delivery of liposome-entrapped dichloromethylene diphosphonate (L-Cl2MDP). Splenic tissue sections that were immunoperoxidase-stained with mAbs against marginal zone macrophages (MONTS-4), red pulp macrophages (SK39), and neutrophils (SK208) showed that 3 days after L-Cl2MDP treatment, macrophages but not neutrophils were depleted, and circulating neutrophils responded normally to an irritated peritoneum and showed normal phagocytic ability. That is, in response to thioglycollate in the peritoneum, neutrophils migrated in normal numbers to the peritoneal cavity and expressed the normal activation phenotype of high Mac-1 and low Mel-14 Ag levels. These neutrophils also showed normal ability to ingest Candida albicans yeast cells in both in vitro and in vivo assays. However, the spleens from L-Cl2MDP-treated mice lost their ability to bind yeast, which agrees with our previous findings that yeast cells bind specifically to marginal zone macrophages. When macrophage-depleted were systemically challenged with C. albicans, clearance of viable fungal elements from blood was slower, their kidneys had higher recoverable CFU, and both BALB/cByJ and congenitally thymic-deficient (nude) mouse strains did not survive as long as control mice. Mice given L-Cl2MDP recovered most of their macrophage function by 56 days and became normal in their resistance to C. albicans. These results indicate that macrophages play an important role in host resistance to experimental disseminated candidiasis, but the mechanism does not appear to involve T cell functions.
Insights
Macrophages are crucial for host resistance against disseminated candidiasis. Depleting macrophages in mice impaired their ability to clear Candida albicans, highlighting their essential role in fighting this fungal infection.
Area of Science:
- Immunology
- Mycology
- Infectious Disease
Background:
- Macrophages are key immune cells involved in host defense.
- Disseminated candidiasis is a serious fungal infection that can be life-threatening.
Purpose of the Study:
- To investigate the specific role of macrophages in experimental disseminated candidiasis.
- To determine if T cell functions are involved in macrophage-mediated resistance.
Main Methods:
- Mice splenic macrophages were depleted using liposome-entrapped dichloromethylene diphosphonate (L-Cl2MDP).
- Immune cell populations (macrophages, neutrophils) were analyzed via immunoperoxidase staining.
- Neutrophil function (migration, phagocytosis) and yeast cell binding to spleen tissue were assessed.
- Macrophage-depleted mice were infected with Candida albicans and survival rates were monitored.
Main Results:
- Macrophage depletion was confirmed, while neutrophil function remained intact.
- Spleens from depleted mice showed reduced yeast cell binding capacity.
- Macrophage-depleted mice exhibited slower fungal clearance, higher kidney fungal loads, and reduced survival rates.
- Macrophage function and resistance to candidiasis were restored by 56 days post-treatment.
Conclusions:
- Macrophages play a critical role in host resistance to experimental disseminated candidiasis.
- The protective mechanism of macrophages in this model does not appear to involve T cell functions.