(515) 280-3100
Veterinary Microbiology
Written by: Riley Holman • 2019 Scholar
The complex interplay between stress and bacterial infections in animals.
Abstract:
Stress -> glucocorticoids, catecholamines and neuroendocrine factors released into circulation Chronic stress -> shifts T helper 1- mediated cellular immunity to T helper 2 mediated humoral. This shift can increase susceptibility of host infection.
Introduction:
- Stress = stimulus to brain that activates sympathetic nervous system
- Chronic stress increases susceptibility to infection by suppressing the immune system What is released when stressed?
- Catecholamines (norepinephrine and epinephrine) via SNS.
- Most important and fast acting
- Glucocorticoids (cortisol and corticosterone) secreted via adrenal gland Hypothalamic-pituitary-adrenal-axis. Slow acting
- Microbial endocrinology = microbiology and neurophysiology intersect to become new research area
- Stress-related hormones affect the pathogenic microorganism itself or the host-pathogen interaction directly GIT, Respiratory, or skin bacteria activate the neuroendocrine stress response
- Stress factors: inadequate housing, overcrowding, heat, cold, poor nutrition, transportation
- Increase pathogen carriage, disease susceptibility, carcass contamination and pathogen shedding
Stress and stress-related hormones:
- Stressors can be different depending on the species or individual, however stress response is the same.
- Activation of SNS and hypothalamic-pituitary-adrenal axis-> catecholamines-> glucocorticoids
Activation of the SNS: catacholamines
- Stress-> SNS->acetylcholine from pre-gang sympathetic fibers->adrenal medulla->epinephrine->bloodstream->SNS nerve terminals-> lymphoid organs
- Catecholamines (epi and NE) bind to adrenergic GPCRs: alpha 1 and 2, beta 1, 2, and 3 subtypes
- All lymphoid cells express beta adrenergic (beta 2 is most important)
- GTP guanosine triphosphate stimulates production of cAMP-> modulates cytokine expression
Activation of the hypothalamic-pituitary-adrenal axis: glucocorticoids
- Stress->hypothalamus secretes corticotropin releasing factor that binds subtype 1 receptors located on anterior pituitary-> ant. pit then releases ACTH into systemic circulation-> triggers glucocorticoid (cortisol) secretion from adrenal glands ->unbound cortisol crosses cell membrane via passive diffusion
- Glucocorticoids regulate wide range of functions: growth, metabolism, cardiovascular system, and immune modulation
- Stress hormones can have a direct effect on all cells of the immune system because they all have receptors for cortisol
Effects of stress on the innate and acquired immune system
- Chronic stress: stimulates humoral (antibody) immunity Inhibits cellular (T-cell) immunity
- Inhibits cellular (T-cell) immunity by switching the cytokine majority from type-1 to type 2...increases risk of infection
- Glucocorticoids suppress IL-12 production via APCs and down-regulate IL-12 receptor expression on NKs and T-cells
- TH1 is down regulated d/t IFN-y secretion
- IL-1, IL-2, IL-6, IL-8, IL-11, and macrophage colony-stimulating factor are suppressed, as well
- Upregulate anti-inflammatory cytokines IL-4 and IL-10 production
- Stress increases the IL-10 production by Th2 cells
Effects of stress on the intestinal barrier
- Enteric nervous system controls GIT
- Linked with CNS via sympathetic and parasympathetic
- Intestinal barrier function: control nutrient uptake while protecting against noxious agents
- Many cellular targets for glucocorticoids and catecholamines...stress mediators lead to bacterial invasion via altering commensal bacteria or altering mucosal integrity
- Commensal bacteria-bacteriocin production (antimicrobial), alter pH
- Mucous layer- physical barrier
- Enterocytes- tight junctions for epithelial transport
- Epithelium- antimicrobial peptides and barrier
- Lamina propria- Enteric NS, endocrine system, immune system, intestinal motility
- NE -> myenteric plexus (submucosa and mucosa) -> increases motility -> flushes out microbiota = pot. Pathogen exp
The effects of stress-related hormones on course of bacterial infections
- Catecholamines stimulate bacterial growth and virulence (bacteria respond via quorum sensing)
Escherichia coli
- Normal inhabitant of GIT in mammals, birds and reptiles
- Includes commensal and virulent E. coli
- Enterotoxogenic E. coli (ETEC)-> watery diarrhea from NE stimulating growth
- Enterohemorrhagic E. coli (EHEC)-> hemorrhagic colitis and haemolytic uremic syndrome. Zoonotic Iron- bacteria need iron for growth and survival...host will dec. iron availability as defense
- But catecholamines remove iron form host and make them available for bacteria and increase biofilms
Salmonella enterica
- Salmonella Typhimurium most predominat serovar in pigs
- Salmonella Enteritidis egg contaminator in birds
- Systemic infections can cause encephalopathy in cattle
- NE-> increases bacterial replication by increasing iron availability->increases risk of contaminating others
Campylobacter jejuni
- Commensal colonies in intestines of chickens, turkeys, duck and pigs
- Most common bacterial cause of food-borne disease (industrial countries)
- Stress induced pathogenesis unknown
- C. jejuni expresses CfrA ferric enterobactin receptor to eventually use as iron source Horizontal transmission
Mycobacteria
- Macrophages are first line of defense
- Adrenergic receptors influence whether macrophages are activated or suppressed by catecholamines
- (stress hormones affect the outcome of mycobacterial infections by suppressing the macrophage-pathogen interaction) M. avium subsp. paratuberculosis-> dec. milk production in ruminants, weight loss, diarrhea without clinical signs during long incubation
Staphylococcus epidermis
NE stimulates biofilm proliferation
Stress response isn’t confined to just pathogens...affects commensal bacteria/microflora Coagulase-negative staphylococci protect against pathogens (S. aureus) and serves as a probiotic
Conclusion
- Stress alters bacterial infections d/t host dependency and bacterium pathogenicity
- In vitro studies prove catecholamines and glucocorticoids increase virulence and growth of many bacterial species
Factors
- Duration of stress
- Host’s immunity
- Virulence of pathogen
- Amount of pathogen exposure
Acute stress- enhanced host cell-mediated immunity (quick T-cell response)
Chronic stress- suppressed cell-mediated immunity...infection is dependent on chronic exposure to stress. Stress can increase biofilms and resistance of E. coli to antimicrobials. Animal welfare is crucial to minimizing stress.
