AAHA

6110 Creston Avenue
Des Moines, Iowa 50321
Phone(515) 280-3100

ISU Student Experience

Veterinary Microbiology

Written by: Riley Holman


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.


View All Scholars


IVS Partner's in Progress CE Event 2019

On April 3, 2019 there were twenty-one speakers offering the second annual ISU – IVS Partners in Progress CE Event at the Des Moines Botanical Center. This CE Event was open to all... read more >

Dr. Greene, one of three boarded oncologists in Iowa, discusses cancer and chemotherapy.

Dr. Greene, one of three boarded oncologists in Iowa, discusses cancer and chemotherapy. read more >

"All the Vet techs and receptionists were nothing but phenomenal and soooo understanding!"

read more testimonials >

AAHA