Macrophages are the determinant of resistance to and outcome of nonlethal Babesia microti infection in mice.

In the present study, we examined the contributions of macrophages to the outcome of infection with Babesia microti, the etiological agent of human and rodent babesiosis, in BALB/c mice. Mice were treated with clodronate liposome at different times during the course of B. microti infection in order to deplete the macrophages. Notably, a depletion of host macrophages at the early and acute phases of infection caused a significant elevation of parasitemia associated with remarkable mortality in the mice. The depletion of macrophages at the resolving and latent phases of infection resulted in an immediate and temporal exacerbation of parasitemia coupled with mortality in mice. Reconstituting clodronate liposome-treated mice at the acute phase of infection with macrophages from naive mice resulted in a slight reduction in parasitemia with improved survival compared to that of mice that received the drug alone. These results indicate that macrophages play a crucial role in the control of and resistance to B. microti infection in mice. Moreover, analyses of host immune responses revealed that macrophage-depleted mice diminished their production of Th1 cell cytokines, including gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). Furthermore, depletion of macrophages at different times exaggerated the pathogenesis of the infection in deficient IFN-γ(-/-) and severe combined immunodeficiency (SCID) mice. Collectively, our data provide important clues about the role of macrophages in the resistance and control of B. microti and imply that the severity of the infection in immunocompromised patients might be due to impairment of macrophage function.

Immunohistochemical study on the ontogenetic development of the regional distribution of peptide YY, pancreatic polypeptide, and glucagon-like peptide 1 endocrine cells in bovine gastrointestinal tract.

The regional distribution and relative frequency of peptide YY (PYY)-, pancreatic polypeptide (PP)-, and glucagon-like peptide 1 (GLP-1)-immunoreactive (IR) cells were determined immunohistochemically in the gastrointestinal tract at seven ontogenetic stages in pre- and postnatal cattle. Different frequencies of PYY-, PP-, and GLP-1-IR cells were found in the intestines at all stages; they were not found in the esophagus and stomach. The frequencies varied depending on the intestinal segment and the developmental stage. The frequencies of PYY- and PP-IR cells were lower in the small intestine and increased from ileum to rectum, whereas GLP-1-IR cells were more numerous in duodenum and jejunum, decreased in ileum and cecum, and increased again in colon and rectum. The frequencies also varied according to pre- and postnatal stages. All three cell types were most numerous in fetus, and decreased in calf and adult groups, indicating that the frequencies of these three types of endocrine cells decrease with postnatal development. The results suggest that these changes vary depending on feeding habits and adaptation of growth, secretion, and motility of intestine at different ontogenetic stages of cattle.

The developmental plasticity of colocalization pattern of peptide YY and glucagon-like peptide-1 in the endocrine cells of bovine rectum.

Peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) are produced in endocrine cells that show distal distribution in each of small and large intestine. They are colocalized in the same endocrine cells at different ratios depending on the animal species. The present study examined the possibility of plasticity in the colocalization pattern in the bovine rectum, which is known to contain endocrine cells at a high concentration. Consecutive sections from different pre- and postnatal stages were stained immunohistochemically. The immunoreactive (IR) cells were divided into three groups: 1) cells IR for both PYY and GLP-1 (PYY/GLP-1-IR cells), 2) cells IR only for PYY (PYY-IR cells), and 3) cells IR only for GLP-1 (GLP-1-IR cells). The percentage of PYY/GLP-1-IR cells was high in the prenatal (early, mid- and late fetuses) and suckling stages, whereas it decreased in the herbivorous (weaning, weaned and adult) stages. In contrast, percentages of PYY and GLP-1-IR single cells were low in the prenatal and suckling stages and increased after the suckling stage. PYY/GLP-1 endocrine cells may adapt to the change of digestion depending on feeding habits and/or specific developmental stages of cattle. The present results suggest the developmental plasticity of the colocalization pattern of gut hormones with nutritional transition.