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Target cell limitation constrains chlamydial load in persistent infections: results from mathematical modelling

Andrew P Craig1, Roger G Rank2, Anne K Bowlin2

  • 1The Kirby Institute, UNSW Australia, Sydney, NSW, Australia.

Pathogens and Disease
|July 22, 2014
PubMed

Insights

In persistent chlamydial infections, the pathogen load stabilizes regardless of initial dose. Target cell availability critically influences infection dynamics and persistence.

Area of Science:

  • Immunology
  • Microbiology
  • Mathematical Biology

Background:

  • Host-pathogen interactions determine infection outcomes.
  • Nonresolving infections in immunodeficient hosts offer insights into persistent infection mechanisms.

Purpose of the Study:

  • To mathematically model and experimentally validate the equilibrium dynamics of persistent Chlamydia muridarum infections.
  • To investigate the influence of inoculum size and target cell availability on infection persistence.

Main Methods:

  • Development of a mathematical model to predict chlamydial load at equilibrium.
  • Experimental infection of RAG(-/-) mice with varying doses of Chlamydia muridarum (10^4-10^7 IFU).
  • Quantification of inclusion-forming units (IFU) at equilibrium.

Main Results:

  • Mathematical model predicted a stable, inoculum-independent equilibrium for chlamydial numbers.
  • Experimental data supported the model's prediction, showing no significant difference in equilibrium IFU levels across inoculation groups.
  • Model estimation indicated only 3% of chlamydiae infect target cells at equilibrium.
  • Equilibrium IFU levels demonstrated high sensitivity to the rate of healthy target cell replenishment.

Conclusions:

  • Inoculum size does not affect the equilibrium level of persistent chlamydial infections.
  • Target cell limitation is a critical factor driving infection dynamics, influencing both peak infection and persistent levels.
  • Findings suggest target cell availability is a key determinant in human chlamydial infections.
Keywords:
Chlamydiaimmunodeficientmathematical modelmousepersistence

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