A systemic inflammatory state with increased circulating tumor necrosis factor alpha (TNF-α) has been related to the bacterial infection susceptibility and hemodynamic derangement of patients with cirrhosis. We compared the activation status of immune cell subpopulations defined by 4-color cytometry in mesenteric and peripheral lymph nodes and blood of rats with CCl₄-cirrhosis to define the immune response initiation site, the T-cell and monocyte contribution to pro-inflammatory cytokine production, as well as the pathogenic role of enteric bacteria in the cirrhosis immune response. Th1 cells and monocytes were expanded in the mesenteric nodes (P < .001) and blood (P < .001) of rats with cirrhosis, and activated to produce interferon gamma (P < .0001) and TNF-α (P < .0001), respectively. The greater numbers of recently activated CD134⁺ Th cells in mesenteric nodes compared with blood, the correlation between their numbers in mesenteric nodes and blood (r = 0.66, P < .001), and the expansion of activated CD45RC⁻ Th cells, which are unable to re-enter lymph nodes, in mesenteric nodes but not in blood or axillary nodes points to mesenteric nodes as the origin site of activated Th cells. Abrogation of bacterial translocation by bowel decontamination reduced the number of activated Th cells and monocytes, and normalized interferon gamma production by Th cells and TNF-α production by monocytes in mesenteric nodes and blood, respectively. In conclusion, in cirrhosis, enteric bacteria start off an orchestrated immune response cascade in mesenteric nodes involving Th1 polarization and monocyte activation to TNF-α production. Later, the recirculation of these activated effector immune cells into blood promotes systemic inflammation. (HEPATOLOGY 2005;42:411–419.)

Systemic activation of the inflammatory immune system contributes to the progression of cir-rhosis with ascites. Immune cells become activated after interacting at the mesenteric lymph nodes (MLNs) with bacteria translocated from the gut, and thereafter reach the bloodstream through recirculation. It is unknown whether systemic activation of the immune system is present in pre-ascitic cirrhosis, in which gut bacterial translocation has not been described. The purpose of this study was to determine whether systemic activation of the immune sys-tem initiates in rats with compensated carbon tetrachloride (CCl ₄ )-induced cirrhosis, and if so to establish the activation site of immune cells. We studied the activation status of immune cells in peripheral blood, MLNs, and hepatic lymph nodes (HLNs). Systemic inflammation was present in rats with cirrhosis, as shown by expansion ( P < 0.01) of circulating total and inflammatory monocytes and recently activated CD134 ¹ T helper (T _h ) cells. The same popu-lations of cells were increased ( P < 0.01) in MLNs and HLNs. Bacterial translocation was absent in rats with cirrhosis or control rats, but bacterial DNA fragments were present in the MLNs of 54% of rats with cirrhosis. The liver was the source of activated immune cells pres-ent in the blood, as shown by the direct correlation between activated T _h cells in the blood and HLNs, but not in MLNs, and the normalization by gut decontamination with antibiotics of activated cells in MLNs, but not in the blood or HLNs. Conclusion: In experimental cir-rhosis, systemic activation of the immune system occurs before ascites development and is driven by recirculation of cells activated in HLNs. In addition, in compensated cirrhosis, bacterial DNA fragments reach the MLNs, where they elicit a local inflammatory response. (HEPATOLOGY 2010;52:2086-2095)

Limited information on the presence of bacterial and hematozoan infections in parasitic arthropods from Spain is available. In an attempt to address this issue, the prevalence of Theileria, Babesia, Hepatozoon, and Rickettsia species was investigated by polymerase chain reaction plus sequencing. In a survey for zoonotic pathogens in ectoparasites, 42 wild animals (which included rodents, carnivores, Sciuridae, and Cervidae) were captured in Burgos (Spain). A total of 256 arthropods (including 107 ticks, 76 fleas, and 73 mites) were collected from these mammals. Molecular diagnostic results showed that (i) Rickettsia felis was found in fleas (two Ctenocephalides felis), (ii) Hepatozoon sp. infected some fleas (two Ctenophtalmus sp. and a DNA pool of Ceratophyllus sciurorum) and Acari (one Neotrombicula sp.), and (iii) Theileria annae was found in Ixodes ricinus and I. hexagonus (each a single infected specimen). All microorganisms and parasites were genetically identical to pathogens already described in Spain or elsewhere. Infected arthropods were recovered from beech marten, bank vole, squirrel, wood mouse, and red fox. Our findings emphasize the potential risk for transmission of rickettsias to humans (namely, R. felis) in Burgos, since C. felis is capable to seek out humans for feeding. No hemoprotozoa with proven significance as human pathogens were found in the survey. However, finding T. annae in ticks recovered from wild canids suggests possible links of sylvatic and domestic cycles for some Piroplasmida.

To clarify the presence of lymphocytic choriomeningitis virus (LCMV) in Spain, we examined blood and tissue specimens from 866 small mammals. LCMV RNA was detected in 3 of 694 wood mice (Apodemus sylvaticus). Phylogenetic analyses suggest that the strains constitute a new evolutionary lineage. LCMV antibodies were detected in 4 of 10 rodent species tested.