No abstract

The murine mammary carcinoma 4T1 causes a leukemoid reaction with profound granulocytosis coincident with the production of tumour-derived growth factors. Here, we study the evolving cellular landscape of primary tumours and metastatic tumour foci and correlate haematopoietic cell infiltration with the production of tumour-derived chemokines. Flow cytometric analysis of enzyme digested primary tumours at different times after transplantation revealed a progressively increasing CD45(+) haematopoietic cell infiltrate consisting predominantly of CD11b(+) myeloid cells. Most of these cells had an F4/80(+)/CD11c(+) phenotype, many of which also stained Gr-1(+). Smaller numbers of Gr-1(+)CD11b(+) granulocytes and lymphoid cells were also identified. Progressive increases in Gr-1(+) granulocytes were observed in enzymatic digests of livers and lungs with metastatic tumour foci. Cultured 4T1 tumour cells expressed mRNA transcripts for the myeloid cell chemokines RANTES, MCP-1 and KC, and enzymatically digested cells from primary 4T1 tumours partially depleted of CD45(+) cells expressed transcripts for these chemokines and also MIP-1alpha and MIP-1beta. These data demonstrate that 4T1 tumour-bearing mice have mixed myeloid cell infiltrates of primary tumours and granulocytic infiltrates of metastatic organs. This pathologic presentation correlated with the expression of tumour-derived chemokines.

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SummaryVertebrate immune systems are understood to be complex and dynamic, with trade-offs among different physiological components (e.g., innate and adaptive immunity) within individuals and among taxonomic lineages. Desert tortoises (Gopherus agassizii) immunised with ovalbumin (OVA) showed a clear trade-off between levels of natural antibodies (NAbs; innate immune function) and the production of acquired antibodies (adaptive immune function). Once initiated, acquired antibody responses included a long-term elevation in antibodies persisting for more than one year. The occurrence of either (a) high levels of NAbs or (b) long-term elevations of acquired antibodies in individual tortoises suggests that long-term humoral resistance to pathogens may be especially important in this species, as well as in other vertebrates with slow metabolic rates, concomitantly slow primary adaptive immune responses, and long life-spans.

Most research of upper respiratory tract disease (mycoplasmal URTD) in the threatened Mojave Desert tortoise (Gopherus agassizii) has worked under the hypothesis that the pathogen, Mycoplasma agassizii, has a relatively consistent and predictable effect on tortoise populations across their natural range. In contrast, we hypothesized that multiple factors influence the prevalence of disease and analyzed biological and environmental variables that vary significantly across the Mojave Desert. We used multiple regression models to analyze associations between mycoplasmal URTD and the genetic structure of 24 tortoise populations, levels of natural antibody (NAb) to M. agassizii in tortoises (one component of the innate immune system), precipitation, and colder thermal regimes. We detected a significant, positive association between mean levels of NAb and seroprevalence to M. agassizii. We hypothesized that NAbs may provide tolerance to mycoplasmal infections and that more tolerant populations may act as host reservoirs of disease. We also detected significant associations between colder winters and mycoplasmal URTD, suggesting that colder winters may depress tortoise immune resistance against M. agassizii or enhance conditions for the growth of M. agassizii.