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Updated: Jan 23, 2026
Alveolar Macrophage Phagocytosis and Bacteria Clearance in Mice
Published on: March 2, 2019
An endosomal LAPF is required for macrophage endocytosis and elimination of bacteria
Tianliang Li1, Kewei Qin1, Nan Li1
1National Key Laboratory of Medical Immunology, Institute of Immunology, Second Military Medical University, 200433 Shanghai, China.
Abstract:
Macrophages can internalize the invading pathogens by raft/caveolae and/or clathrin-dependent endocytosis and elicit an immune response against infection. However, the molecular mechanism for macrophage endocytosis remains elusive. Here we report that LAPF (lysosome-associated and apoptosis-inducing protein containing PH and FYVE domains) is required for caveolae-mediated endocytosis. Lapf-deficient macrophages have impaired capacity to endocytose and eliminate bacteria. Macrophage-specific Lapf-deficient mice are more susceptible to Escherichia coli (E. coli) infection with higher bacterial loads. Moreover, Lapf deficiency impairs TLR4 endocytosis, resulting in attenuated production of TLR-triggered proinflammatory cytokines. LAPF is localized to early endosomes and interacts with caveolin-1. Phosphorylation of LAPF by the tyrosine kinase Src is required for LAPF-Src-Caveolin complex formation and endocytosis and elimination of bacteria. Collectively, our work demonstrates that LAPF is critical for endocytosis of bacteria and induction of inflammatory responses, suggesting that LAPF and Src could be potential targets for the control of infectious diseases.
Insights
Lysosome-associated and apoptosis-inducing protein containing PH and FYVE domains (LAPF) is crucial for macrophage endocytosis of bacteria. LAPF deficiency impairs bacterial clearance and immune responses, highlighting its role in infectious disease control.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Macrophages internalize pathogens via endocytosis to mount immune responses.
- The precise molecular mechanisms governing macrophage endocytosis are not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanisms of macrophage endocytosis.
- To identify key proteins involved in pathogen internalization and immune response.
Main Methods:
- Investigated lysosome-associated and apoptosis-inducing protein containing PH and FYVE domains (LAPF) function in macrophages.
- Utilized LAPF-deficient macrophages and macrophage-specific LAPF-deficient mice.
- Examined bacterial endocytosis, clearance, and Toll-like receptor 4 (TLR4) signaling.
Main Results:
- LAPF is essential for caveolae-mediated endocytosis of bacteria by macrophages.
- LAPF-deficient macrophages exhibit impaired bacterial uptake and elimination.
- LAPF deficiency leads to increased susceptibility to *Escherichia coli* infection and reduced TLR4-mediated cytokine production.
- LAPF interacts with caveolin-1 and requires Src-mediated phosphorylation for its function.
Conclusions:
- LAPF plays a critical role in bacterial endocytosis and the subsequent inflammatory response.
- LAPF and the tyrosine kinase Src are potential therapeutic targets for managing infectious diseases.
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