). After four Dehydrogenase inhibitor days the phages 1 × 106 and bacteria (5 × 106) were administered. The mice were bled for the measurement of antibody titer 21 days later. The number of mice was 10 per group. Statistics: CP-P-B- vs CP-P-B+ P = 0.0495; CP-P-B+ vs CP+P-B+ P = 0.0369; CP+P-B+ vs CP+P+B+ P = 0.0001 (ANOVA of Kruskal-Wallis; P = 0.0000). Discussion The results presented in this report demonstrated
not only efficient removal of the bacterial load in infected mice virtually devoid of major functional phagocytes, by prophylactic administration of specific phages, but also revealed accompanying, beneficial effects on the immune find more system, mediated by S. aureus phage preparation in the described model. It appeared that application of phages in infected mice may accelerate renewal of cells depleted by CP treatment, both of the myelocytic and lymphocytic lineages. The first type of cells has significance in the first-line defense against bacteria as phagocytes and the latter differentiate to mature, immunocompetent cells, giving rise to adaptive, antigen-specific immune response. It is conceivable that the stimulation of hematopoiesis by phages is initiated by destruction of bacterial walls and release of bacterial antigens acting as PLX4032 adjuvants for the immune system.
The stimulatory effects of different bacterial antigens on hematopoiesis in CP-immunosuppressed mice were reported by others [33, 34]. The increased stimulation of hematopoiesis in infected, phage-treated (CP+P+B+) mice versus infected (CP+P-B+) mice or mice treated only with phages (CP+P+B-), found in this
study, supports such a notion. In infected mice not treated with CP, the phages elevated the percentage of mature neutrophils (segments) (CP-P+B+ versus CP-P-B+ mice), although not significantly. That phenomenon could represent an additional output of mature neutrophils from the bone marrow reservoir which is particularly large in rodents . The infection of acetylcholine CP-treated mice (CP+P-B+ group) resulted in a characteristic change in the blood picture with appearance of immature and mature neutrophils as well as more immature cells from myelo- and lymphocytic lineages. The proportion of these cell types, including a small contribution of eosinophils and monocytes, significantly increased in mice treated additionally with phages (from 40.4 to 70.2%) (Figure 3). The effective killing of bacteria in the investigated organs, particularly in the liver, where most of the killing takes place , probably resulted from the increased number of phagocytes, as shown in this work, although we assume that a contribution of phages in that process is the major one. The bone marrow picture in normal mice showed a significant increase of the mature neutrophils content after infection (CP-P-B+ group), with a reduction in these cells upon phage application that suggests an accelerated export of neutrophils into periphery.