Innate immunity — Lactoferrin, a multifunctional host glycoprotein found in tears, saliva, milk, and neutrophil granules, helps protect against pathogenic microbes primarily by which mechanism?

Introduction / Context:
Lactoferrin is an iron-binding glycoprotein that contributes to the innate immune defense on mucosal surfaces and within neutrophil secondary granules. Because many pathogens require freely available iron for growth and for key redox enzymes, limiting iron availability is a powerful, host-driven antimicrobial strategy. This question tests understanding of the primary protective mechanism of lactoferrin and distinguishes it from other nonspecific defenses like acidity or commensal competition.

Given Data / Assumptions:

• Lactoferrin is present in secretions such as tears, saliva, and milk, and is released by activated neutrophils.
• Pathogens depend on bioavailable ferric or ferrous iron for replication.
• We compare mechanisms: iron sequestration versus pH change, sebum effects, or commensal growth promotion.

Concept / Approach:
Lactoferrin tightly chelates iron, reducing the concentration of free iron in the local environment. This creates a bacteriostatic effect because iron-dependent enzymes and respiratory pathways are impaired. In addition, lactoferrin can disrupt biofilms, bind to lipopolysaccharide, and modulate immune responses, but the best known and most fundamental antimicrobial action is nutrient sequestration of iron. Lowering pH is primarily achieved by organic acids and gastric acid, while modulation of sebum is unrelated, and commensal growth promotion is an indirect consequence rather than the main mode of action.

Step-by-Step Solution:

Verification / Alternative check:
Experimental systems show growth inhibition of common pathogens in the presence of apolactoferrin; addition of excess iron reverses this inhibition, confirming that iron withdrawal is the key factor rather than direct cytotoxicity.

Why Other Options Are Wrong:

• Blocking sebum production: sebum is a skin lipid secretion; lactoferrin does not block its production.
• Lowering the pH: acidification is a general defense but is not the principal action of lactoferrin.
• Facilitating normal flora: commensals may benefit secondarily, but this is not the primary biochemical mechanism.

Common Pitfalls:
Assuming all secreted antimicrobial proteins act by membrane disruption; lactoferrin mainly starves microbes of iron, with additional modulatory effects.

Final Answer:
sequestering Iron