Neutrophils (PMN) have been described as critical effector cells in the host's antibacterial innate immunities. However, the classification of murine PMNs remains unclear. Here, we show that in addition to normal PMN (PMN-N), there are at least two distinct subsets of PMNs (PMN-I and PMN-II) distinguished as follows: (1) cytokine and chemokine production (PMN-I, IL-12/CCL3; PMN-II, IL-10/CCL2; PMN-N, no cytokine/chemokine production), (2) macrophage activation (PMN-I, classically activated macrophages; PMN-II, alternatively activated macrophages; PMN-N, no effect on macrophage activation), (3) Toll-like receptor (TLR) expression (PMN-I, TLR2/TLR4/TLR5/TLR8; PMN-II, TLR2/TLR4/TLR7/TLR9; PMN-N, TLR2/TLR4/TLR9), and (4) surface antigen expression (PMN-I, CD49d(+)CD11b-; PMN-II, CD49d(-)CD11b+; PMN-N, CD49d(-)CD11b-). PMN-I was obtained from MRSA (methicillin-resistant Staphylococcus aureus)-resistant hosts, while MRSA-sensitive hosts were a source of PMN-II. PMN-N was obtained from naive mice. Anti-MRSA innate immunities might be influenced differently by these biochemically and physically distinguished PMNs. PMN-N may convert to PMN-I or PMN-II in response to host circumstance.

Chronic alcohol consumption markedly impairs host antibacterial defense against opportunistic infections. γ-irradiated NOD-SCID IL-2Rγnull mice inoculated with nonalcoholic PBMCs (control PBMC chimeras) resisted Klebsiella pneumonia and gut bacteria-associated sepsis, whereas the chimeras created with alcoholic PBMCs (alcoholic PBMC chimeras) were very susceptible to these infections. M1 monocytes (IL-12+IL-10−CD163−CD14+ cells), major effector cells in antibacterial innate immunity, were not induced by a bacterial Ag in alcoholic PBMC cultures, and M2b monocytes (CCL1+CD163+CD14+ cells), which predominated in alcoholic PBMCs, were shown to be inhibitor cells on the Ag-stimulated monocyte conversion from quiescent monocytes to M1 monocytes. CCL1, which functions to maintain M2b macrophage properties, was produced by M2b monocytes isolated from alcoholic PBMCs. These M2b monocytes reverted to quiescent monocytes (IL-12−IL-10−CCL1−CD163−CD14+ cells) in cultures supplemented with CCL1 antisense oligodeoxynucleotide, and the subsequent quiescent monocytes easily converted to M1 monocytes under bacterial Ag stimulation. Alcoholic PBMC chimeras treated with CCL1 antisense oligodeoxynucleotide were resistant against pulmonary infection by K. pneumoniae and sepsis stemming from enterococcal translocation. These results indicate that a majority of monocytes polarize to an M2b phenotype in association with alcohol abuse, and this polarization contributes to the increased susceptibility of alcoholics to gut and lung infections. Bacterial pneumonia and gut bacteria-associated sepsis, frequently seen in alcoholics, can be controlled through the polarization of macrophage phenotypes.

Nonalcoholic fatty liver disease (NAFLD) can develop into end-stage disease that includes cryptogenic cirrhosis and hepatocellular carcinoma. Bacterial endotoxin, for example lipopolysaccharide (LPS), plays an important role in the pathogenesis of NAFLD. The aim of this study was to assess the role of LPS in the development of NAFLD. Twenty-one male Zucker (fa/fa) rats were divided into three groups: rats fed for twelve weeks on a diet rich in disaccharide (D12 group), rats similarly managed but treated with LPS (LPS group), and those on the same diet for 24 weeks (D24 group). Histological examination demonstrated that this protocol induced hepatic steatosis in the LPS and D24 groups. Significant, marked accumulation of lipid droplets was observed in the LPS group, compared with the D24 group. Rats from the LPS group showed a decrease in plasma adiponectin levels, an increase in plasma leptin levels, and greater expression of FAS and SREBP-1c mRNA in the liver, compared with rats from the D24 group. These finding coincided with histological findings. We therefore suggest that LPS may accelerate the progression of hepatic steatosis.

Mphi-associated host antibacterial innate immunities are greatly influenced by SIRS levels. CAMphi, effector cells for the antibacterial innate immunity against E. faecalis, MRSA, and CLP-induced sepsis, are induced in mild SIRS mice. AAMphi with no antibacterial capabilities are generated in mice with severe SIRS. Induction of CAMphi may protect severe SIRS patients against infections.