The acute hyperplasia in calves was characterized

by an approximate fourfold greater increase in large versus small splenic leucocytes. The variation noted in these leucocyte measurements probably results from sampling a relatively small piece of spleen and the disproportionate increase in red pulp postinfection. Despite this limitation, these results are consistent with a local immune response of naïve animals to acute haemoparasite infection and reflect the central importance of large leucocytes – monocytes/macrophages, DCs and NK cells – to the spleen-dependent immune response of naïve calves to B. bovis infection (31). In addition to these gross changes in click here splenic composition, Tamoxifen manufacturer changes were also observed in the distribution of phenotyped cells within and between the domains

of the spleen (summarized in Table 3). Regarding the splenic distribution of large leucocyte populations during acute B. bovis infection, observations with functional implications include the following: (i) loss of the relative accumulation of NK cells (CD335+) within the marginal zone, (ii) unambiguous early redistribution of iDCs (CD13+) to the junction of the marginal zone with follicles and PALS, (iii) subsequent juxtaposed appearance of an immunologically important B. bovis surface antigen (MSA-1+), and (iv) restriction of monocyte/macrophage (CD172a+) hyperplasia to within the red pulp. The marginal zone is a complex environment in which cell trafficking and interaction with blood-borne foreign antigens takes place (32,33). Within the spleen of uninfected calves, iDCs were present as a network-like distribution covering the marginal zone and red pulp whereas NK cells appeared to accumulate only within the marginal

zone. Crosstalk between NK cells and DCs is crucial to the innate immune response (34–37), and in mice Anidulafungin (LY303366) involves secretion of IL-15 by DCs (38), which primes NK cells to produce IFN-γ, which in turn increases DC activity (39). Similarly, we have previously shown up-regulation of IL-15 mRNA in the spleen of calves early after infection with B. bovis (15) and in vitro crosstalk that requires NK cell-iDC contact (13). Given the initial co-population of the marginal zone with CD335+ and CD13+ cells, it is possible that the first 4–6 days of B. bovis infection in calves involves critical NK/iDC crosstalk and activation. The unambiguous redistribution of iDCs to the junction between marginal zones, follicles and PALS is consistent with the immunological importance placed on NK/DC crosstalk. As such, early activation with narrow redistribution to these junctions by 7 dpi may optimally position iDCs to encounter B. bovis merozoites and infected erythrocytes as they enter the parenchyma of the spleen.