The immune response of inbred laboratory mice to Litomosoides sigmodontis: A route to discovery in myeloid cell biology

Abstract

Litomosoides sigmodontis is the only filarial nematode where the full life cycle, from larval delivery to the skin through to circulating microfilaria, can be completed in immunocompetent laboratory mice. It is thus an invaluable tool for the study of filariasis. It has been used for the study of novel anti‐helminthic therapeutics, the development of vaccines against filariasis, the development of immunomodulatory drugs for the treatment of inflammatory disease and the study of basic immune responses to filarial nematodes. This review will focus on the latter and aims to summarize how the L sigmodontis model has advanced our basic understanding of immune responses to helminths, led to major discoveries in macrophage biology and provided new insights into the immunological functions of the pleural cavity. Finally, and most importantly L sigmodontis represents a suitable platform to study how host genotype affects immune responses, with the potential for further discovery in myeloid cell biology and beyond.

Microfilaria-dependent thoracic pathology associated with eosinophilic and fibrotic polyps in filaria-infected rodents

“…The immune response in the thoracic cavity between the two pleurae has been extensively characterized at different stages of the filarial infection from the arrival of L3 larvae in the pleural space to the patent phase in susceptible (BALB/c) and resistant (C57BL/6) mouse models [ 15 , 29 , 31 , 43 – 45 ]. Depending on the mouse strain, the mode of infection (natural through the vector or inoculation of a known number of L3) and the amount of the inoculum, the intensity of cell recruitment and the secretions of specific cytokines are different [ 25 , 29 , 46 – 48 ]. Regarding the mode of infection, subcutaneous (SC) injection of L3 may circumvent some of the skin immune responses and later pathological responses in the thoracic cavity.…”

Human filariasis—contributions of the Litomosoides sigmodontis and Acanthocheilonema viteae animal model

“…List of publications was generated via PubMed search (see supplement table 1 for search parameters and complete list) and assigned one main topic each 2019). For a more in-depth review of immune responses to L. sigmodontis in mice, we refer the reader to the recent review by Finlay and Allen (2020).…”

“…Key results that helped to facilitate experimental studies include improvements to the laboratory maintenance and in particular generation of large numbers of L3 larvae via the “pelting method” (McCall 1976 ), dissection of mites (Nakamura et al 1984 ), isolation of L3 larvae from the pleural cavity of Mongolian jirds 5 days after the infection (Hübner et al 2009 ), and the validation of mice as an experimental host (Hawking and Burroughs 1946 ; Patra and Basu 1970 ; Petit et al 1992 ). Mice have become the main experimental host for immunological research since the seminal paper by Petit et al ( 1992 ) showed the susceptibility and maturation of L. sigmodontis in mice with a BALB/c background (Hoffmann et al 2000 ; Finlay and Allen 2020 ). An overview about publications on L. sigmodontis is shown in Fig.…”

“…BALB/c mice which develop a patent infection show a hyporesponsive phenotype compared to C57BL/6 mice (Finlay and Allen 2020 ). This difference in responsiveness appears to be strongly dependent on an expansion of regulatory T cells which suppresses the immune response to L. sigmodontis (Taylor et al 2005 , 2007 , 2012 ).…”

“…al. 2005 ; Finlay and Allen 2020 ). In addition to hyporesponsive CD4+ T cells (Knipper et al 2019 ; Haben et al 2013 ; van der Werf et al 2013 ), cytotoxic T cell responses were also shown to be inhibited during L. sigmodontis infection (Kolbaum et al 2012 ; Buerfent et al 2015 ).…”