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Host Defense and Parasite Evasion
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
The IL-25 released by tufts cells, along with the other alarmins, also appears to be involved in the activation of immune system cells called type 2 innate lymphoid (ILC2) cells. These novel lymphocytes lack conventional TCRs. They were first discovered in 2010 in the lymph nodes of Nippostrongylus brasiliensis-infected mice. Their role in Th-2 immunity is at least 2-fold; first, once activated, ILC2 cells secrete IL-13, which stimulates undifferentiated epithelial cells to differentiate into tuft cells, increasing their number. Production of IL-25 thus rises, resulting in a positive feedback loop between tuft cells and ILC2 cells. Second, once naïve CD4+ T cells have recognized their antigen, presented by dendritic cells, IL-13 along with IL-5 and IL-4, released by activated ILC2 cells helps drive the differentiation of these CD4+ cells into Th-2 cells. Other cells, including mast cells and basophils, also release IL-4 and thus may play a role in driving the differentiation of CD4+ T cells toward the Th-2 phenotype. The relative importance of these various sources of IL-4 remains under investigation.
Macrophages As Effectors Of Cell-Mediated Immunity
Published in Hans H. Gadebusch, Phagocytes and Cellular Immunity, 2020
The expulsion of intestinal parasites, such as Nippostrongylus brasiliensis and Tri-chostrongylus colubriformis, by experimental animals (rats and guinea pigs) is an immunological phenomenon. Both humoral and cell-mediated immune mechanisms appear to be involved in a collaborative process,147,171,172 but the role, if any, of macrophages as effectors is unknown.
Mucosal responses to helminth infections
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
William Gause, Richard Grencis
Our understanding of the mechanisms of resistance and susceptibility to infection by helminth parasites has largely been determined through the use of infections in laboratory rodents, notably the mouse (see later sections). These have been extremely informative at defining the roles of various immune cells and molecules involved in protective immunity. By controlling conditions and infection levels (that are impossible to do in the field), these models have generated clear insight into how protective immunity can operate against these large multicellular parasites. Extensive use has been made of Nippostrongylus brasiliensis, which is a natural roundworm parasite of the rat but that also readily infects mice and exhibits many of the features of human hookworm in that it infects via skin penetration by the L3 larval stage and migrates through the lungs prior to residence in the small intestine. In mice, this infection is readily expelled during the intestinal phase of infection and animals become resistant to subsequent infection.
Cytotoxic furanosesquiterpenoids and steroids from Ircinia mutans sponges
Published in Pharmaceutical Biology, 2021
Fatemeh Heidary Jamebozorgi, Morteza Yousefzadi, Omidreza Firuzi, Melika Nazemi, Somayeh Zare, Jima N. Chandran, Bernd Schneider, Ian T. Baldwin, Amir Reza Jassbi
Furanosesquiterpenes are an outstanding group of natural products that have been isolated from both terrestrial and marine organisms including sponges, cnidaria (especially class anthozoa), and molluscs (Fontana et al. 1995; Arepalli et al. 2009; Rajaram et al. 2013). Tubipofuran and 15-acetoxytubipofuran are examples of cytotoxic marine furanosesquiterpenoids, isolated from the organ pipe coral (Tubipora musica Linnaeus, Tubiporidae), which have shown ichthyotoxicity against killifish Oryzias latipes (IC50 15 μg/mL and 20 μg/mL respectively), and the latter has also shown cytotoxicity against B-16 melanoma cells in vitro (IC50 33 μg/mL) (Iguchi et al. 1986). (-)-Furodysinin is antiparasitic against the tested organism Nippostrongylus brasiliensis Travassos (Heligmonellidae) in vitro but inactive against two others N. dubius Baylis (Heligmosomidae) and Hypselodoris nana (Chromodorididae) in vivo test above 1000 ppm (Horton et al. 1990). The furanoid-sesquiterpenes furodysin and furodysinin previously were isolated from sponges Dysidea herbacea Keller (Dysideidae) and Dysidea fragilis Montagu (Dysideidae) (Kazlauskas et al. 1978; Dunlop et al. 1982; Su et al. 2010), but to the best of our knowledge, their cytotoxic activity has not been investigated.
Helminth–virus interactions: determinants of coinfection outcomes
Published in Gut Microbes, 2021
Pritesh Desai, Michael S. Diamond, Larissa B. Thackray
Some human helminths such as A. lumbricoides, A. duodenale, and N. americanus have an extraintestinal phase in which the larvae migrate through different tissues such as the lungs before reaching the GI tract. As a surrogate to examine the effects of such helminths on viral infection, Ascaris suum (A. suum) and Nippostrongylus brasiliensis (N. brasiliensis) are used as models in mice. An earlier study found that coinfection of mice with A. suum and influenza virus resulted in adverse clinical outcomes.71 In comparison to mice infected with influenza virus alone that caused 30% mortality, coinfection resulted in 90% mortality. Moreover, the coinfected mice also died sooner than mice infected with influenza alone (5 versus 7 days) and showed pronounced dyspnea. Similar observations were made when mice were coinfected with N. brasiliensis and influenza virus.20 Coinfected mice showed higher mortality (26% vs. 6%) and greater lung consolidation scores (41% vs. 26%) compared to mice infected with the influenza virus alone. These findings suggest that a connection with helminths that traverse through the lungs and respiratory viruses can be detrimental to the host. However, the precise mechanism by which these lung-traversing helminths impact the pathogenesis of respiratory viruses and disease outcomes has not been elucidated.
Comparative Analysis of Bone Marrow-derived Mast Cell Differentiation in C57BL/6 and BALB/c Mice
Published in Immunological Investigations, 2019
Miki Nagashima, Madoka Koyanagi, Yutaka Arimura
In contrast to allergy, in which mast cells have detrimental effects, mast cells appear to be required for host defense against helminth and bacterial infection. Expulsion of adult Trichinella spiralis and Nippostrongylus brasiliensis from the intestinal tract is delayed in mast cell-deficient W/Wv mice (Crowle and Reed, 1981; Ha et al., 1983; Mitchell et al., 1983). These reports clearly indicate a requirement of mast cells. A molecular mechanism for the expulsion of T. spiralis has been attributed to mast cell protease (MCP)-1 release from cytoplasmic granules of mast cells (Knight et al., 2000). MCP-6 contributes to eosinophil recruitment upon T. spiralis infection (Shin et al., 2008) as well as neutrophil recruitment upon Klebsiella pneumoniae infection (Thakurdas et al., 2007). Mast cells also recruit neutrophils via tumor necrosis factor alpha (TNF-α) production in delayed-type hypersensitivity reactions (Biedermann et al., 2000) and indirectly in experimental peritonitis through macrophage inflammatory protein-2 (MIP-2) (Mercer-Jones et al., 1999).