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Escherichia coli K1 inhibits proinflammatory cytokine induction in monocytes by preventing NF‐κB activation
Author(s) -
Selvaraj Suresh K.,
Prasadarao Nemani V.
Publication year - 2005
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0904516
Subject(s) - proinflammatory cytokine , biology , chemokine , mapk/erk pathway , tumor necrosis factor alpha , p38 mitogen activated protein kinases , cytokine , monocyte , microbiology and biotechnology , kinase , lipopolysaccharide , nf κb , signal transduction , inflammation , immunology
Phagocytes are well‐known effectors of the innate immune system to produce proinflammatory cytokines and chemokines such as tumor necrosis factor α (TNF‐α), interleukin (IL)‐1β, and IL‐8 during infections. Here, we show that infection of monocytes with wild‐type Escherichia coli K1, which causes meningitis in neonates, suppresses the production of cytokines and chemokines (TNF‐α, regulated on activation, normal T expressed and secreted, macrophage‐inflammatory protein‐1β, IL‐1β, and IL‐8). In contrast, infection of monocytes with a mutant E. coli , which lacks outer membrane protein A (OmpA– E. coli ) resulted in robust production of cytokines and chemokines. Wild‐type E. coli K1 (OmpA+ E. coli ) prevented the phosphorylation and its degradation of inhibitor of κB, thereby blocking the translocation of nuclear factor (NF)‐κB to the nucleus. OmpA+ E. coli ‐infected cells, subsequently subjected to lipopolysaccharide challenge, were crippled severely in their ability to activate NF‐κB to induce cytokine/chemokine production. Selective inhibitors of the extracellular signal‐regulated kinase (ERK) 1/2 pathway and p38 mitogen‐activated protein kinase (MAPK), but not Jun N‐terminal kinase, significantly reduced the activation of NF‐κB and the production of cytokines and chemokines induced by OmpA– E. coli , indicating a role for these kinases in the NF‐κB/cytokine pathway. It is interesting that the phosphorylation of ERK 1/2 and p38 MAPK was notably reduced in monocytes infected with OmpA+ E. coli when compared with monocytes infected with OmpA– E. coli , suggesting that the modulation of upstream events common for NF‐κB and MAPKs by the bacterium is possible. The ability of OmpA+ E. coli K1 to inhibit the macrophage response temporarily may enable bacterial survival and growth within the host for the onset of meningitis by E. coli K1.