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| Content Provider | PubMed Central |
|---|---|
| Author | Luo, Yong Isaac, Beth M. Casadevall, Arturo Cox, Dianne |
| Abstract | Cryptococcus neoformans is the only encapsulated human-pathogenic fungus and a facultative intracellular pathogen that can reside in macrophages without host cell lysis. In the present study, we investigated how phagocytosis of C. neoformans affected the macrophage response to chemoattractants such as fractalkine (FKN) (CX3CL1) and colony-stimulating factor 1 (CSF-1). Phagocytosis of immunoglobulin G (IgG)-opsonized C. neoformans and IgG- or C3bi-opsonized sheep erythrocytes was performed using a RAW 264.7 subline (LR5 cells) and bone marrow-derived macrophages (BMM). The chemotactic response to FKN or CSF-1 was quantitated by measurement of the formation of F-actin-enriched membrane protrusions (ruffles), which showed that FKN or CSF-1 stimulated strong transient ruffling in both LR5 cells and BMM. This stimulated cell ruffling was inhibited by phagocytosis in an intracellular-pathogen-number-dependent manner. The inhibition of ruffling was not simply a result of reduced membrane availability since membrane sequestration by sucrose treatment did not inhibit the ruffling response. The phagocytosis process was required to inhibit ruffling as BMM from FcγR−/− mice that bound C. neoformans but did not ingest it retained the ability to ruffle in response to chemoattractants. These results imply that the inhibition of FKN- or CSF-1-stimulated cell ruffling was a direct consequence of the phagocytosis process. Since cell ruffling is a prelude to chemotaxis, this observation links two functions of macrophages that are critical to host defense, chemotaxis and phagocytosis. Phagocytosis-induced chemotactic suppression may enhance host defense by keeping these antimicrobial effector cells at infected sites and reduce the likelihood of microbial spread by wandering macrophages containing infectious cargo. |
| Related Links | http://dx.doi.org/10.1128/iai.00530-09 |
| Ending Page | 4495 |
| Page Count | 9 |
| Starting Page | 4487 |
| File Format | |
| ISSN | 00199567 |
| e-ISSN | 10985522 |
| Journal | Infection and Immunity |
| Issue Number | 10 |
| Volume Number | 77 |
| Language | English |
| Publisher | American Society for Microbiology (ASM) |
| Publisher Date | 2009-10-01 |
| Access Restriction | Open |
| Rights Holder | American Society for Microbiology (ASM) |
| Subject Keyword | Immunology Microbiology Parasitology Infectious Diseases Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Infectious Diseases Parasitology Immunology Microbiology |
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