RESUMO
Although dietary macronutrients are known to regulate insect immunity, few studies have examined their evolutionary effects. Here, we evaluate this relationship in the cricket Gryllodes sigillatus by maintaining replicate populations on four diets differing in protein (P) to carbohydrate (C) ratio (P- or C-biased) and nutritional content (low- or high-nutrition) for >37 generations. We split each population into two; one maintained on their evolution diet and the other switched to their ancestral diet. We also maintained populations exclusively on the ancestral diet (baseline). After three generations, we measured three immune parameters in males and females from each population. Immunity was higher on P-biased than C-biased diets and on low- versus high-nutrition diets, although the latter was most likely driven by compensatory feeding. These patterns persisted in populations switched to their ancestral diet, indicating genetic divergence. Crickets evolving on C-biased diets had lower immunity than the baseline, whereas their P-biased counterparts had similar or higher immunity than the baseline, indicating that populations evolved with dietary manipulation. Although females exhibited superior immunity for all assays, the sexes showed similar immune changes across diets. Our work highlights the important role that macronutrient intake plays in the evolution of immunity in the sexes.
Assuntos
Gryllidae , Animais , Feminino , Masculino , Gryllidae/genética , Dieta , Nutrientes , ImunidadeRESUMO
Insects are important models for studying immunity in an ecological and evolutionary context. Yet, most empirical work on the insect immune system has come from phenotypic studies meaning we have a limited understanding of the genetic architecture of immune function in the sexes. We use nine highly inbred lines to thoroughly examine the genetic relationships between a suite of commonly used immune assays (haemocyte count, implant encapsulation, total phenoloxidase activity, antibacterial zone of inhibition and pathogen clearance) and resistance to infection by three generalist insect pathogens (the gram-negative bacterium Serratia marcescens, the gram-positive bacterium Bacillus cereus and the fungus Metarhizium robertsii) in male and female Gryllodes sigillatus. There were consistent positive genetic correlations between haemocyte count, antibacterial and phenoloxidase activity and resistance to S. marcescens in both sexes, but these relationships were less consistent for resistance to B. cereus and M. robertsii. In addition, the clearance of S. marcescens was genetically correlated with the resistance to all three pathogens in both sexes. Genetic correlations between resistances to the different pathogen species were inconsistent, indicating that resistance to one pathogen does not necessarily mean resistance to another. Finally, while there is ample genetic (co)variance in immune assays and pathogen resistance, these genetic estimates differed across the sexes and many of these measures were not genetically correlated across the sexes, suggesting that these measures could evolve independently in the sexes. Our finding that the genetic architecture of immune function is sex and pathogen specific suggests that the evolution of immune function in male and female G. sigillatus is likely to be complex. Similar quantitative genetic studies that measure a large number of assays and resistance to multiple pathogens in both sexes are needed to ascertain if this complexity extends to other species.
Assuntos
Gryllidae , Animais , Antibacterianos , Feminino , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Gryllidae/fisiologia , Masculino , Monofenol Mono-Oxigenase/genéticaRESUMO
Dietary macronutrients regulate life span and aging, yet little is known about their evolutionary effects. Here, we examine the evolutionary response of these traits in decorated crickets (Gryllodes sigillatus) maintained on diets varying in caloric content and protein-to-carbohydrate ratio. After 37 generations, each population was split: half remained on the evolution diet, and half switched to a standardized diet. Crickets lived longer and aged slower when evolving on high-calorie (both sexes) and carbohydrate-biased (females only) diets and had lower baseline mortality on high-calorie (females only) diets. However, on the standardized diet, crickets lived longer when evolving on high-calorie diets (both sexes), aged slower on high-calorie (females only) and carbohydrate-biased (both sexes) diets, and had lower baseline mortality on high-calorie (males only) and protein-biased (both sexes) diets. Life span was longer, and baseline mortality was lower when provided with the evolution vs. the standardized diet, but the aging rate was comparable. Moreover, life span was longer, aging slower (females only), and baseline mortality was lower (males only) compared to our evolved baseline, suggesting varying degrees of dietary adaptation. Collectively, we show dietary components influence the evolution of life span and aging in different ways and highlight the value of combining experimental evolution with nutritional geometry.
Assuntos
Envelhecimento , Evolução Biológica , Dieta , Gryllidae , Longevidade , Animais , Gryllidae/fisiologia , Gryllidae/genética , Feminino , Masculino , Nutrientes/metabolismo , Carboidratos da Dieta , Proteínas Alimentares , Ingestão de EnergiaRESUMO
With respect to salmonid aquaculture, one of the most important bacterial pathogens due to high mortality and antibiotic usage is the causative agent of typical furunculosis, Aeromonas salmonicida spp. salmonicida (Asal). In Atlantic salmon, Salmo salar, the host response during infections with Asal is well-documented, with furunculosis outbreaks resulting in significant mortality in commercial settings. However, less is known about the host-pathogen interactions in the emerging aquaculture species, Arctic charr Salvelinus alpinus. Furthermore, there is no data on the efficacy or response of this species after vaccination with commonly administered vaccines against furunculosis. To this end, we examined the immunological response of S. alpinus during infection with Asal, with or without administration of vaccines (Forte Micro®, Forte Micro® + Renogen®, Elanco Animal Health). Artic charr (vaccinated or unvaccinated) were i.p.-injected with a virulent strain of Asal (106 CFUs/mL) and tissues were collected pre-infection/post-vaccination, 8, and 29 days post-infection. Unvaccinated Arctic charr were susceptible to Asal with 72% mortalities observed after 31 days. However, there was 72-82% protection in fish vaccinated with either the single or dual-vaccine, respectively. Protection in vaccinated fish was concordant with significantly higher serum IgM concentrations, and following RNA sequencing and transcriptome assembly, differential expression analysis revealed several patterns and pathways associated with the improved survival of vaccinated fish. Most striking was the dramatically higher basal expression of complement/coagulation factors, acute phase-proteins, and iron hemostasis proteins in pre-challenged, vaccinated fish. Remarkably, following Asal infection, this response was abrogated and instead the transcriptome was characterized by a lack of immune-stimulation compared to that of unvaccinated fish. Furthermore, where pathways of actin assembly and FcγR-mediated phagocytosis were significantly differentially regulated in unvaccinated fish, vaccinated fish showed either the opposite regulation (ForteMicro®), or no impact at all (ForteMicro®Renogen®). The present data indicates that vaccine-induced protection against Asal relies on the pre-activation and immediate control of humoral immune parameters that is coincident with reduced activation of apoptotic (e.g., NF-κB) and actin-associated pathways.
Assuntos
Aeromonas salmonicida/metabolismo , Aeromonas salmonicida/patogenicidade , Furunculose/microbiologia , Infecções por Bactérias Gram-Negativas , Imunidade Humoral , Truta/imunologia , Vacinação , Actinas/metabolismo , Animais , Aquicultura , Proteínas do Sistema Complemento/genética , Furunculose/prevenção & controle , Sequenciamento de Nucleotídeos em Larga Escala , Interações Hospedeiro-Patógeno , Imunoglobulina M/sangue , NF-kappa B/metabolismo , Fagocitose/imunologia , Análise de Sequência de RNA , Transcriptoma , Resultado do Tratamento , Truta/genéticaRESUMO
Streptococcus suis is an important swine pathogen and emerging zoonotic agent. Encapsulated strains of S. suis modulate dendritic cell (DC) functions, leading to poorly activated CD4+ T cells. However, the antigen presentation ability of S. suis-stimulated DCs has not been investigated yet. In this work, we aimed to characterize the antigen presentation profiles of S. suis-stimulated DCs, both in vitro and in vivo. Upon direct activation in vitro, S. suis-stimulated murine bone marrow-derived DCs (bmDCs) preserved their antigen capture/processing capacities. However, they showed delayed kinetics of MHC-II expression compared to lipopolysaccharide-stimulated bmDCs. Meanwhile, splenic DCs from infected mice exhibited a compromised MHC-II expression, despite an appropriate expression of maturation markers. To identify potential interfering mechanisms, Class II Major Histocompatibility Complex Transactivator (CIITA) and membrane-associated RING-CH (MARCH)1/8 transcription were studied. S. suis-stimulated DCs maintained low levels of CIITA at early time points, both in vitro and in vivo, which could limit their ability to increase MHC-II synthesis. S. suis-stimulated DCs also displayed sustained/upregulated levels of MARCH1/8, thus possibly leading to MHC-II lysosomal degradation. The bacterial capsular polysaccharide played a partial role in this modulation. Finally, interleukin (IL)-12p70 production was inhibited in splenic DCs from infected mice, a profile compatible with DC indirect activation by pro-inflammatory compounds. Consequently, these cells induced lower levels of IL-2 and TNF-α in an antigen-specific CD4+ T cell presentation assay and blunted T cell CD25 expression. It remains unclear at this stage whether these phenotypical and transcriptional modulations observed in response to S. suis in in vivo infections are part of a bacterial immune evasion strategy or rather a feature common to systemic inflammatory response-inducing agents. However, it appears that the MHC-II-restricted antigen presentation and Th1-polarizing cytokine production capacities of DCs are impaired during S. suis infection. This study highlights the potential consequences of inflammation on the type and magnitude of the immune response elicited by a pathogen.
Assuntos
Células Dendríticas/imunologia , Interleucina-12/metabolismo , Infecções Estreptocócicas/imunologia , Streptococcus suis/fisiologia , Células Th1/imunologia , Animais , Apresentação de Antígeno , Diferenciação Celular , Células Cultivadas , Citocinas/metabolismo , Feminino , Antígenos de Histocompatibilidade Classe II/metabolismo , Evasão da Resposta Imune , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Sorogrupo , Transativadores/genética , Transativadores/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Streptococcus suis and Haemophilus parasuis are normal inhabitants of the porcine upper respiratory tract but are also among the most frequent causes of disease in weaned piglets worldwide, causing inflammatory diseases such as septicemia, meningitis and pneumonia. Using an in vitro model of infection with tracheal epithelial cells or primary alveolar macrophages (PAMs), it was possible to determine the interaction between S. suis serotype 2 and H. parasuis strains with different level of virulence. Within H. parasuis strains, the low-virulence F9 strain showed higher adhesion levels to respiratory epithelial cells and greater association levels to PAMs than the high-virulence Nagasaki strain. Accordingly, the low-virulence F9 strain induced, in general, higher levels of pro-inflammatory cytokines than the virulent Nagasaki strain from both cell types. In general, S. suis adhesion levels to respiratory epithelial cells were similar to H. parasuis Nagasaki strain. Yet, S. suis strains induced a significantly lower level of pro-inflammatory cytokine expression from epithelial cells and PAMs than those observed with both H. parasuis strains. Finally, this study has shown that, overall and under the conditions used in the present study, S. suis and H. parasuis have limited in vitro interactions between them and use probably different host receptors, regardless to their level of virulence.
RESUMO
Group B Streptococcus (GBS) serotype III causes life-threatening infections. Cytokines have emerged as important players for the control of disease, particularly IFN-γ. Although potential sources of this cytokine have been proposed, no specific cell line has ever been described as a leading contributor. In this study, CD4(+) T cell activation profiles in response to GBS were evaluated through in vivo, ex vivo, and in vitro approaches. Total splenocytes readily produce a type 1 proinflammatory response by releasing IFN-γ, TNF-α, and IL-6 and actively recruit T cells via chemokines like CXCL9, CXCL10, and CCL3. Responding CD4(+) T cells differentiate into Th1 cells producing large amounts of IFN-γ, TNF-α, and IL-2. In vitro studies using dendritic cell and CD4(+) T cell cocultures infected with wild-type GBS or a nonencapsulated mutant suggested that GBS capsular polysaccharide, one of the major bacterial virulence factors, differentially modulates surface expression of CD69 and IFN-γ production. Overall, CD4(+) T cells are important producers of IFN-γ and might thus influence the course of GBS infection through the expression balance of this cytokine.
Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Interferon gama/imunologia , Polissacarídeos Bacterianos/farmacologia , Infecções Estreptocócicas/imunologia , Streptococcus agalactiae/imunologia , Animais , Antígenos CD/genética , Antígenos CD/imunologia , Antígenos de Diferenciação de Linfócitos T/genética , Antígenos de Diferenciação de Linfócitos T/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Diferenciação Celular/efeitos dos fármacos , Quimiocina CCL3/genética , Quimiocina CCL3/imunologia , Quimiocina CXCL10/genética , Quimiocina CXCL10/imunologia , Quimiocina CXCL9/genética , Quimiocina CXCL9/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/patologia , Feminino , Regulação da Expressão Gênica , Interferon gama/genética , Interleucina-2/genética , Interleucina-2/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Lectinas Tipo C/genética , Lectinas Tipo C/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Polissacarídeos Bacterianos/biossíntese , Transdução de Sinais , Baço/efeitos dos fármacos , Baço/imunologia , Baço/patologia , Infecções Estreptocócicas/genética , Infecções Estreptocócicas/microbiologia , Infecções Estreptocócicas/mortalidade , Streptococcus agalactiae/metabolismo , Streptococcus agalactiae/patogenicidade , Análise de Sobrevida , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
The pathogenesis of Streptococcus suis infection, a major swine and human pathogen, is only partially understood and knowledge on the host adaptive immune response is critically scarce. Yet, S. suis virulence factors, particularly its capsular polysaccharide (CPS), enable this bacterium to modulate dendritic cell (DC) functions and potentially impair the immune response. This study aimed to evaluate modulation of T cell activation during S. suis infection and the role of DCs in this response. S. suis-stimulated total mouse splenocytes readily produced TNF-α, IL-6, IFN-γ, CCL3, CXCL9, and IL-10. Ex vivo and in vivo analyses revealed the involvement of CD4+ T cells and a Th1 response. Nevertheless, during S. suis infection, levels of the Th1-derived cytokines TNF-α and IFN-γ were very low. A transient splenic depletion of CD4+ T cells and a poor memory response were also observed. Moreover, CD4+ T cells secreted IL-10 and failed to up-regulate optimal levels of CD40L and CD69 in coculture with DCs. The CPS hampered release of several T cell-derived cytokines in vitro. Finally, a correlation was established between severe clinical signs of S. suis disease and impaired antibody responses. Altogether, these results suggest S. suis interferes with the adaptive immune response.