All Posts Tagged With: "macrophages"

Current thinking emphasizes the primacy of CD14 in facilitating
recognition of microbes by certain TLRs to initiate pro-inflammatory
signaling events and the importance of p38-MAPK in augmenting such
responses. Herein, this paradigm is challenged by demonstrating that
recognition of live Borrelia burgdorferi not only triggers an
inflammatory response in the absence of CD14, but one that is, in part,
a consequence of altered PI3K/AKT/p38-MAPK signaling and impaired
negative regulation of TLR2. CD14 deficiency results in increased
localization of PI3K to lipid rafts, hyperphosphorylation of AKT, and
reduced activation of p38. Such aberrant signaling leads to decreased
negative regulation by SOCS1, SOCS3, and CIS, thereby compromising the
induction of tolerance in macrophages and engendering more severe and
persistent inflammatory responses to B. burgdorferi. Importantly, these
altered signaling events and the higher cytokine production observed can
be mimicked through shRNA and pharmacological inhibition of p38 activity
in CD14-expressing macrophages. Perturbation of this
CD14/p38-MAPK-dependent immune regulation may underlie development of
infectious chronic inflammatory syndromes.
 

Abstract: The life transmission cycle of B. burgdorferi requires migration of spirochetes from tick’s gut to its salivary glands during vertebrate’s blood sucking, penetrating to the vertebrate’s tissues and their colonization. A special feature of these bacteria, despite
its relatively small genome, is the ability to adapt in different host environments. Continued

Genetic control of the innate immune response to Borrelia hermsii influences the course of relapsing fever in inbred strains of mice.

Benoit VM, Petrich A, Alugupalli KR, Marty-Roix R, Moter A, Leong JM, Boyartchuk VL.

Department of Molecular Genetics and Microbiology, and Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605; Institut für Mikrobiologie und Hygiene, Charité – Universitätsmedizin Berlin, Campus Charité Mitte, 10117 Berlin, Germany; Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107. Continued

Klemen Strle,1
Elise E. Drouin,1
Shiqian Shen,1
Joseph El Khoury,1,2
Gail McHugh,1
Eva Ruzic‐Sabljic,3
Franc Strle,4 and
Allen C. Steere1

Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, 2Infectious Diseases Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; and 3Institute of Microbiology and Immunology, University of Ljubljana, 4Department of Infectious Diseases, University Medical Center Ljubljana, Ljubljana, Slovenia Continued