Intracellular innate resistance to bacterial pathogens

Abstract

SummaryMammalian innate immunity stimulates antigenspecific immune responses and acts to control infection prior to the onset of adaptive immunity. Some bacterial pathogens replicate within the host cell and are therefore sheltered from some protective aspects of innate immunity such as complement. Here we focus on mechanisms of innate intracellular resistance encountered by bacterial pathogens and how some bacteria can evade destruction by the innate immune system. Major strategies of intracellular antibacterial defence include pathogen compartmentalization and iron limitation. Compartmentalization of pathogens within the host endocytic pathway is critical for generating high local concentrations of antimicrobial molecules, such as reactive oxygen species, and regulating concentrations of divalent cations that are essential for microbial growth. Cytosolic sensing, autophagy, sequestration of essential nutrients and membrane attack by antimicrobial peptides are also discussed.

Interleukin 10 suppresses lysosome-mediated killing of Brucella abortus in cultured macrophages

“…Different members of cathepsins including CtsB, CtsD, CtsG, CtsL and CtsS are known to interact and contribute to killing intracellular Mycobacterium tuberculosis (20,21), Mycobacterium bovis (22), Streptococcus pneumoniae (23) and Listeria monocytogenes (24). Additionally, HexB was also proven to protect macrophage against Mycobacterium marinum (25) in macrophages.…”

Critical Role for Transcription Factor C/EBP-β in Regulating the Expression of Death-Associated Protein Kinase 1

“…However, in response to these escapees, the immune system activates autophagy, which targets intracellular bacteria for sequestration within autophagosomes, ultimately delivering them to the lysosomes, where they are destroyed. IFN-␥ induces autophagy (22,61), which inhibits the growth of intracellular bacterial pathogens and some viruses (29,43,62,68). Interestingly, one of the major defects in cebpb Ϫ/Ϫ mice is the inability of macrophages to kill intracellular bacterial and fungal pathogens (72,82,95) and heterologous tumors due to defective phagocytic activity.…”

NAIP and Ipaf Control Legionella pneumophila Replication in Human Cells

“…Sensing by these receptors activates signaling cascades finally leading to the production of inflammatory mediators, recruitment of phagocytic cells, and to control of the acquired immune response (10 -12). Additionally, innate intracellular resistance activities exist in different cell types and are particularly important for controlling intracellular bacterial infections (13)(14)(15). The mechanisms and the regulation of the innate intracellular defense against bacterial pathogens are, however, not well understood.…”