In vitro derivation of macrophage from guinea pig bone marrow with human M-CSF

The guinea pig has a storied history as a model in the study of infectious disease and immunology. Because of reproducibility of data and availability of various reagents, inbred mice have since supplanted the guinea pig as the animal model-of-choice in these fields. However, several clinically-significant microorganisms do not cause the same pathology in mice, or mice may not be susceptible to these infections. These demonstrate the utility of other animal models — either as the primary method to study a particular infection, or to confirm or refute findings in the mouse before translating basic science into clinical practice.The mononuclear phagocyte, or macrophage (Mφ), plays a key role in antigen presentation and the pathogenesis of intracellular bacteria, such as Mycobacterium tuberculosis and Legionella pneumophila. Because of variable yield and difficult extraction from tissue, the preferred method of producing Mφ for in vitro studies is to expand murine bone marrow (BM) precursors with mouse macrophage colony-stimulating factor (M-CSF). This has not been shown in the guinea pig. Here, we report the empiric observation that human M-CSF – but not mouse M-CSF, nor human granulocyte/macrophage colony-stimulating factor – can be used to induce BM precursor differentiation into bonafide Mφ. The differentiated cells appeared as enlarged adherent cells, capable of both pinocytosis and large particle phagocytosis. Furthermore, we showed that these guinea pig BM-derived Mφ, similar to human monocyte/Mφ lines but unlike most murine BM Mφ, support growth of wild type L. pneumophila.This method may prove useful for in vitro studies of Mφ in the guinea pig, as well as in the translation of results found using mouse BM-derived Mφ towards studies in human immunology and infectious disease.