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Host ICAMs play a role in cell invasion by Mycobacterium tuberculosis and Plasmodium falciparum

Kuhulika Bhalla1, Monika Chugh2, Sonali Mehrotra2

  • 1Recombinant Gene Products Group, International Centre for Genetic Engineering and Biotechnology, ICGEB, Aruna Asaf Ali Marg, New Delhi 110067, India.

Nature Communications
|January 15, 2015
PubMed

Insights

A synthetic protein, M5, targets intercellular adhesion molecules (ICAMs) to block infections by Mycobacterium tuberculosis and Plasmodium falciparum. ICAM-1 and ICAM-4 are key in host cell invasion by these pathogens.

Area of Science:

  • Immunology
  • Infectious Diseases
  • Cell Biology

Background:

  • Intercellular adhesion molecules (ICAMs) are crucial in cellular processes, including host-pathogen interactions.
  • ICAM-1 is found on macrophages, while ICAM-4 is specific to red blood cells.

Purpose of the Study:

  • To investigate the role of ICAM-1 and ICAM-4 in host cell invasion by Mycobacterium tuberculosis and Plasmodium falciparum.
  • To identify molecules that can inhibit pathogen invasion mediated by ICAMs.

Main Methods:

  • In vitro interaction studies, surface plasmon resonance, and immunolocalization were used to characterize the binding of a synthetic protein, M5, to ICAM-1 and ICAM-4.
  • Mycobacterium tuberculosis and Plasmodium falciparum invasion assays were performed.
  • Pharmacological and siRNA-mediated inhibition of ICAM-1 expression was utilized.

Main Results:

  • The synthetic protein M5 binds to both human ICAM-1 and ICAM-4.
  • M5 significantly inhibits the invasion of macrophages by Mycobacterium tuberculosis and erythrocytes by Plasmodium falciparum.
  • Inhibition of ICAM-1 expression reduced Mycobacterium tuberculosis invasion.
  • ICAM-4 was found to bind Plasmodium falciparum merozoites, and its addition blocked erythrocyte invasion.

Conclusions:

  • ICAM-1 and ICAM-4 play significant roles in host cell invasion by Mycobacterium tuberculosis and Plasmodium falciparum, respectively.
  • These ICAMs may function as receptors or accessory molecules in pathogen entry.
  • The synthetic protein M5 shows potential as an inhibitor of these infectious agents.

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