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Abstract Tumors develop in a complex physical, biochemical, and cellular milieu, referred to as the tumor microenvironment. Of special interest is the set of immune cells that reciprocally interact with the tumor, the tumor-immune microenvironment (TIME). The diversity of cell types and cell–cell interactions in the TIME has led researchers to apply concepts from ecology to describe the dynamics. However, while tumor cells are known to induce immune cells to switch from anti-tumor to pro-tumor phenotypes, this type of ecological interaction has been largely overlooked. To address this gap in cancer modeling, we develop a minimal, ecological model of the TIME with immune cell conversion, to highlight this important interaction and explore its consequences. A key finding is that immune conversion increases the range of parameters supporting a co-existence phase in which the immune system and the tumor reach a stalemate. Our results suggest that further investigation of the consequences of immune cell conversion, using detailed, data-driven models, will be critical for greater understanding of TIME dynamics.
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The role of varying resources on Daphnia dentifera immune responses [The role of varying resources on Daphnia dentifera immune responses]
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ABSTRACT In this comprehensive exploration, we delve into the pivotal role of host plants in shaping the intricate interactions between herbivorous insects and their pathogens. Recent decades have seen a surge in studies that demonstrate that host plants are crucial drivers of the interactions between insects and pathogens, providing novel insights into the direct and indirect interactions that shape tri‐trophic interactions. These studies have built on a wide range of pathogens, from viruses to bacteria, and from protozoans to fungi. We summarise these studies, and discuss the mechanisms of plant‐mediated insect resistance to infection, ranging from the toxicity of plant chemicals to pathogens to enhancement of anti‐pathogen immune responses, and modulation of the insect's microbiome. Although we provide evidence for the roles of all these mechanisms, we also point out that the majority of existing studies are phenomenological, describing patterns without addressing the underlying mechanisms. To further our understanding of these tri‐trophic interactions, we therefore urge researchers to design their studies to enable them specifically to distinguish the mechanisms by which plants affect insect susceptibility to pathogens.more » « less
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A within-human-host malaria parasite model, integrating key variables that influence parasite evolution-progression-advancement, under innate and adaptive immune responses, is analyzed. The implicit role of immunity on the steady state parasite loads and parasitemia reproduction number ([Formula: see text]), a threshold parameter measuring the parasite’s annexing ability of healthy red blood cells (HRBCs), eventually rendering a human infectious to mosquitoes, is investigated. The impact of the type of recruitment function used to model HRBC growth is also investigated. The model steady states and [Formula: see text], both obtained as functions of immune system variables, are analyzed at snapshots of immune sizes. Model results indicate that the more the immune cells, innate and adaptive, the more efficient they are at inhibiting parasite development and progression; consequently, the less severe the malaria disease in a patient. Our analysis also illustrates the existence of a Hopf bifurcation leading to a limit cycle, observable only for the nonlinear recruitment functions, at reasonably large [Formula: see text].more » « less
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Abstract The immune and circulatory systems of insects are functionally integrated. Following infection, immune cells called hemocytes aggregate around the ostia (valves) of the heart. An earlier RNA sequencing project in the African malaria mosquito,Anopheles gambiae, revealed that the heart-associated hemocytes, called periostial hemocytes, express transglutaminases more highly than hemocytes elsewhere in the body. Here, we further queried the expression of these transglutaminase genes and examined whether they play a role in heart-associated immune responses. We found that, in the whole body, injury upregulates the expression ofTGase2, whereas infection upregulatesTGase1,TGase2andTGase3. RNAi-based knockdown ofTGase1andTGase2did not alter periostial hemocyte aggregation, but knockdown ofTGase3increased the number of periostial hemocytes during the early stages of infection and the sequestration of melanin by periostial hemocytes during the later stages of infection. In uninfected mosquitoes, knockdown ofTGase3also slightly reduced the number of sessile hemocytes outside of the periostial regions. Taken altogether, these data show thatTGase3negatively regulates periostial hemocyte aggregation, and we hypothesize that this occurs by negatively regulating the immune deficiency pathway and by altering hemocyte adhesion. In conclusion,TGase3is involved in the functional integration between the immune and circulatory systems of mosquitoes.more » « less
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Abstract Host susceptibility may be critical for the spread of infectious disease, and understanding its basis is a goal of ecological immunology. Here, we employed a series of mechanistic tests to evaluate four factors commonly assumed to influence host susceptibility: parasite exposure, barriers to infection, immune responses, and body size. We tested these factors in an aquatic host–parasite system (Daphnia dentifera and the fungal parasite, Metschnikowia bicuspidata) using both laboratory-reared and field-collected hosts. We found support for each factor as a driver of infection. Elevated parasite exposure, which occurs through consumption of infectious fungal spores, increased a host’s probability of infection. The host’s gut epithelium functioned as a barrier to infection, but in the opposite manner from which we predicted: thinner anterior gut epithelia were more resistant to infectious spores than thick epithelia. This relationship may be mediated by structural attributes associated with epithelial cell height. Fungal spores that breached the host’s gut barrier elicited an intensity-dependent hemocyte response that decreased the probability of infection for some Daphnia. Although larger body sizes were associated with increased levels of spore ingestion, larger hosts also had lower frequencies of parasite attack, less penetrable gut barriers, and stronger hemocyte responses. After investigating which mechanisms underlie host susceptibility, we asked: do these four factors contribute equally or asymmetrically to the outcome of infection? An information-theoretic approach revealed that host immune defenses (barriers and immune responses) played the strongest roles in mediating infection outcomes. These two immunological traits may be valuable metrics for linking host susceptibility to the spread of infectious disease.more » « less
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1127/fal/2022/1458
