The integrin Mac-1 (CR3) mediates internalization and directs Bacillus anthracis spores into professional phagocytes

Claudia R Oliva; Melissa K Swiecki; Corinne E Griguer; Mark W Lisanby; Daniel C Bullard; Charles L Turnbough; John F Kearney

doi:10.1073/pnas.0709321105

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The integrin Mac-1 (CR3) mediates internalization and directs Bacillus anthracis spores into professional phagocytes

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The integrin Mac-1 (CR3) mediates internalization and directs Bacillus anthracis spores into professional phagocytes

Claudia R Oliva, Melissa K Swiecki, Corinne E Griguer, Mark W Lisanby, Daniel C Bullard, Charles L Turnbough and John F Kearney

Proceedings of the National Academy of Sciences - PNAS, Vol.105(4), pp.1261-1266

01/29/2008

DOI: 10.1073/pnas.0709321105

PMCID: PMC2234126

PMID: 18216258

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Abstract

Anthrax, a disease caused by Bacillus anthracis , affects animals and humans. Because the inert spore is the infectious form of the organism that first contacts the potential host, the interaction between the host and spore exosporium is vital to the initiation of disease. Here, we demonstrate that the integrin Mac-1 is essential for the recognition of the major exosporium protein BclA by phagocytic cells. Expression of Mac-1, but not p150/95, in CHO cells markedly enhanced infection with Sterne strain of B. anthracis spores (WT spores). Conversely, CD11b −/− macrophages demonstrated a significant decrease in spore uptake when compared with macrophages from normal C57BL/6 mice. However, when CD11b −/− macrophages were infected with Δ bclA spores, spore ingestion was no different from their C57BL/6 counterparts. Δ bclA spores were also efficiently internalized by all CHO cell lines tested, independently of Mac-1 expression. Taken together, these results show that there is an alternative Mac-1-independent pathway involved in spore uptake that is unmasked only in the absence of BclA. Survival studies, using C57BL/6 and CD11b −/− mice, revealed that CD11b −/− mice are more resistant to infection with WT but not Δ bclA spores. Our experiments also show that Δ bclA spores are more virulent than WT spores in C57BL/6 and A/J mice. Overall, our data indicate that the Mac-1/BclA interaction may play a major role in B. anthracis pathogenesis by promoting spore uptake by professional phagocytes and subsequent access to a favorable niche for transport, germination, and outgrowth in lymphoid tissues.

Biological Sciences

Details

Title: Subtitle: The integrin Mac-1 (CR3) mediates internalization and directs Bacillus anthracis spores into professional phagocytes
Creators: Claudia R Oliva - Departments of Microbiology
Melissa K Swiecki - Departments of Microbiology
Corinne E Griguer - Surgery, and
Mark W Lisanby - Departments of Microbiology
Daniel C Bullard - Genetics, University of Alabama at Birmingham, Birmingham, AL 35294-2170
Charles L Turnbough - Departments of Microbiology
John F Kearney - Departments of Microbiology
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.105(4), pp.1261-1266
DOI: 10.1073/pnas.0709321105
PMID: 18216258
PMCID: PMC2234126
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 01/29/2008
Academic Unit: Radiation Oncology
Record Identifier: 9984047681902771

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